WO2019128976A1 - Pyridine sulfone, derivatives thereof, preparation method therefor, and application thereof - Google Patents

Pyridine sulfone, derivatives thereof, preparation method therefor, and application thereof Download PDF

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Publication number
WO2019128976A1
WO2019128976A1 PCT/CN2018/123428 CN2018123428W WO2019128976A1 WO 2019128976 A1 WO2019128976 A1 WO 2019128976A1 CN 2018123428 W CN2018123428 W CN 2018123428W WO 2019128976 A1 WO2019128976 A1 WO 2019128976A1
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Prior art keywords
nitropyridin
amine
compound
formula
alkyl
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PCT/CN2018/123428
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French (fr)
Chinese (zh)
Inventor
刘卫东
柳爱平
刘兴平
李建明
刘民华
何莲
任叶果
项军
马保德
闫忠忠
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湖南化工研究院有限公司
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Publication of WO2019128976A1 publication Critical patent/WO2019128976A1/en

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/61—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/70—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/73—Unsubstituted amino or imino radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to pyridone and its derivatives having bactericidal, insecticidal/industrial activity, and a process for the preparation thereof, a bactericidal, insecticidal/sputum composition containing the same, and the use of these compounds for controlling harmful bacteria, pests/cockroaches Use and method.
  • Sulfone and its derivatives are important compounds in medicinal chemistry. They have a broad spectrum of biological activities. There are many reports on biologically active sulfones and their derivatives, but reports of pyridine sulfone and its derivatives are rare. Even the occasional reports of pyridine sulfone and its derivatives are mostly related to its medicinal activity. Reports of pyridylsulfone and its derivatives active against harmful bacteria and/or pests/caries are not easily found.
  • the sulfone compound represented by the formula (A) as reported in the literature belongs to the field of medicine.
  • Sulfone compounds especially pyridine sulfone and its derivatives, have been one of our research directions in order to obtain novel structural compounds active against harmful bacteria and/or pests/sputums.
  • Applicants have discovered a novel class of pyridylsulfone and its derivatives with broad-spectrum biological activity.
  • the applicant specifically synthesizes the phenyl sulfone represented by the formula (B), the formula (C) and the formula (D) and derivatives thereof and tests the organism thereof. active.
  • the compounds of the present invention not only have significantly different structural characteristics, but also these structural differences allow the compounds of the present invention to have a broader spectrum and superior biological activity, and some compounds such as 29, 244, etc. exhibit a formula (B), (C) and phenyl sulfone and its derivatives represented by formula (D) are more broad-spectrum and more efficient biological activities.
  • the present invention provides a pyridyl sulfone having a biological activity such as a pathogen, a pest, or a cockroach, and a derivative thereof, represented by the formula (I):
  • I.R represents a nitro group
  • R 1 represents hydrogen, C 1 -C 12 alkyl or C 3 -C 6 cycloalkyl
  • R 2 represents hydrogen, halogen, C 1 -C 12 alkyl or C 3 -C 6 cycloalkyl
  • R 3 represents hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or phenyl;
  • VR 4 represents hydrogen, C 1 -C 12 alkyl or C 3 -C 6 cycloalkyl
  • R 5 represents hydrogen, C 1 -C 12 alkyl, C 3 -C 8 cycloalkyl, phenyl, phenylmethyl, phenylethyl, thiazolyl, thiazolylmethyl, thiazolylethyl, Furanyl, furylmethyl, furylethyl, thiophenol, thiophenoxymethyl, thiophenethyl, tetrahydrofuranyl, tetrahydrofuranylmethyl, tetrahydrofuranylethyl, pyridyl, halopyridyl, Pyridylmethyl, halopyridylmethyl, pyridylethyl, halopyridylethyl;
  • n does not represent 0;
  • the compound of the formula (I) does not represent N-ethyl-N-((2-chlorothiazol-5-yl)methyl)-6-methylthio-3-nitropyridin-2-amine and N- Cyclobutyl-6-methylthio-3-nitropyridin-2-amine;
  • Halogen means fluorine, chlorine, bromine, iodine
  • Alkyl means a straight or branched alkyl group
  • Cycloalkyl means a saturated or unsaturated cycloalkyl group
  • Heterocycloalkyl a saturated or unsaturated heterocycloalkyl group having at least one N, O and/or S;
  • Alkenyl means straight or branched and may have a double bond at any position
  • Alkynyl means straight or branched and may have a triple bond at any position.
  • Preferred compounds of the invention are: in formula (I):
  • R 1 represents hydrogen or C 1 -C 12 alkyl
  • R 2 represents hydrogen, halogen or C 1 -C 12 alkyl
  • R 3 represents hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or phenyl;
  • VR 4 represents hydrogen or C 1 -C 12 alkyl
  • R 5 represents hydrogen, C 1 -C 12 alkyl, C 3 -C 8 cycloalkyl, phenyl, phenylmethyl, phenylethyl, thiazolyl, thiazolylmethyl, thiazolylethyl, Furanyl, furylmethyl, furylethyl, thiophenol, thiophenoxymethyl, thiophenethyl, tetrahydrofuranyl, tetrahydrofuranylmethyl, tetrahydrofuranylethyl, pyridyl, halopyridyl, Pyridylmethyl, halopyridylmethyl, pyridylethyl, halopyridylethyl;
  • n does not represent 0;
  • the compound of the formula (I) does not represent N-ethyl-N-((2-chlorothiazol-5-yl)methyl)-6-methylthio-3-nitropyridin-2-amine and N- Cyclobutyl-6-methylthio-3-nitropyridin-2-amine.
  • R 1 represents hydrogen or C 1 -C 12 alkyl
  • R 2 represents hydrogen, halogen or C 1 -C 12 alkyl
  • R 3 represents hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or phenyl;
  • VR 4 represents hydrogen or C 1 -C 12 alkyl
  • R 5 represents hydrogen, C 1 -C 12 alkyl, C 3 -C 8 cycloalkyl, phenyl, phenylmethyl, phenylethyl, thiazolyl, thiazolylmethyl, thiazolylethyl, Furanyl, furylmethyl, furylethyl, thiophenol, thiophenoxymethyl, thiophenethyl, tetrahydrofuranyl, tetrahydrofuranylmethyl, tetrahydrofuranylethyl, pyridyl, halopyridyl, Pyridylmethyl, halopyridylmethyl, pyridylethyl, halopyridylethyl;
  • a still further preferred compound of the invention is: in formula (I):
  • R 1 represents hydrogen or C 1 -C 12 alkyl
  • R 2 represents hydrogen, halogen or C 1 -C 12 alkyl
  • R 3 represents hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or phenyl;
  • VR 4 represents hydrogen or C 1 -C 12 alkyl
  • R 5 represents hydrogen, C 1 -C 12 alkyl, cyclopropyl, phenyl, phenylmethyl, thiazolyl, thiazolylmethyl, furyl, furylmethyl, thiophenol, thiophenol Methyl, tetrahydrofuranyl, tetrahydrofuranylmethyl, pyridyl, halopyridyl, pyridylmethyl, halopyridylmethyl;
  • Preferred compounds of formula (I) according to the invention are:
  • the compounds of the invention may exist in the form of one or more isomers.
  • Isomers include enantiomers, diastereomers, geometric isomers.
  • a compound represented by the formula (I) of the present invention may form a geometric isomer (a different configuration is represented by Z and E, respectively) because a carbon-carbon double bond is bonded to a different substituent, and the present invention includes Z-isomers and E-isomers and mixtures thereof in any ratio.
  • the compound of the formula (I) of the present invention since one of the carbon atoms is bonded to four different substituents to form a stereoisomer (representing different configurations by R and S, respectively), the present invention includes the R form. Isomers and S isomers and mixtures thereof in any ratio.
  • the compounds of the general formula (I) of the present invention and certain compounds disclosed in the prior art belong to pyridyl sulfone and its derivatives, they have significantly different structural features and synthetic methods compared to the prior art. And the difference in these structural features allows the compounds of the present invention to have a broader spectrum and superior biological activity.
  • the compound of the formula (I) exhibits excellent activity against various pathogens in agriculture or other fields, and some compounds also exhibit good activity against weeds or pests/cockroaches. Accordingly, the technical solution of the present invention also includes the use of the compound of the general formula (I) as a bactericide, insecticide/caries agent in agriculture or other fields.
  • the invention further relates to a biologically effective amount of a compound of formula (I) and at least one additional composition selected from the group consisting of surfactants, solid diluents and liquid diluents for controlling harmful bacteria, pests/caries.
  • the invention further relates to a composition
  • a composition comprising a biologically effective amount of a compound of formula (I) and an effective amount of at least one additional biologically active compound or formulation for controlling harmful bacteria, pests/caries.
  • the invention also relates to a method of controlling harmful germs, pests, pests, comprising contacting a biologically effective amount of a compound of formula (I) with a harmful pathogen, pest/sputum or its environment. Also relates to such a harmful pathogen, pest/clam control method, harmful bacteria, pests/sputum or its environmentally effective amount of a compound of formula (I) or a compound containing formula (I) and a biologically effective amount of at least one additional The compound or mixture of preparations is contacted to control harmful bacteria, pests/caries.
  • the compound of the formula (I) of the present invention has a broad spectrum activity at an amount of from 15 to 5000 g of active ingredient per hectare: some compounds can be used for controlling harmful bacteria, and can also be used for controlling pests/cockroaches; and some compounds for certain targets It has a high biological activity, so that good results can be obtained at very low doses.
  • compositions of the invention are compositions containing the preferred compounds described above.
  • a preferred method is the method using the above preferred compounds.
  • the compound of the formula (I) provided by the present invention has biological activity and some compounds have good biological activity, and particularly exhibits activity in the control of agricultural, horticultural, flower and hygienic harmful bacteria and pests/cockroaches.
  • the pests described herein include, but are not limited to, the invention.
  • Oomycetes diseases such as downy mildew, white rust, squatting, cotton rot, blight, late blight, etc.;
  • Semi-bacterial diseases such as blight, root rot, blight, anthracnose, verticillium, scab, gray mold, brown spot, black spot, spot blight, early blight, round disease , leaf blight, stem-based rot, etc.;
  • Basidiomycosis diseases such as rust and smut
  • Ascomycetes such as powdery mildew, sclerotinia sclerotiorum (flax sclerotium, rapeseed sclerotium, soybean sclerotium, peanut sclerotium, tobacco sclerotium, capsicum sclerotium, eggplant sclerotium, bean sclerotium Disease, pea sclerotium disease, cucumber sclerotium disease, bitter gourd sclerotium disease, melon sclerotium disease, watermelon sclerotium disease, celery sclerotium disease, and scab.
  • Orthoptera is like a scorpion, such as cotton scorpion horse, rice scorpion horse, melon scorpion horse, Homoptera such as spider mites, locusts, locusts, lepidoptera such as oriental armyworm, Spodoptera litura, Plutella xylostella, Beet armyworm, Spodoptera litura, Pieris rapae, Hymenoptera such as leaf bee larvae, Diptera such as Aedes aegypti, Culex pipiens, flies; ⁇ such as orange full claw ⁇ , cotton leaf ⁇ , two-leaf ⁇ ;
  • Monocotyledonous weeds such as crabgrass, valerian, foxtail, hard grass, valerian, bromegrass, maiden, wheat, alkali, star grass, wild oats, ryegrass, bentgrass, bluegrass ;
  • Dicotyledonous weeds such as castor, sorghum, longan, scorpion, scorpion, scorpion, chamomile, etc.
  • the compound of the formula (I) of the present invention has excellent activity against rice sheath blight, corn rust, cucumber gray mold, and the like, and has a good control effect at a lower dose.
  • the above compounds can be advantageously used to protect crops, livestock and stocks that are important in agriculture and horticulture, as well as the environment in which humans often go, from the damage of germs, pests and mites.
  • the amount of the compound varies depending on various factors such as the compound used, the preprotectant, the type of the pest, the degree of infection, the climatic conditions, the method of administration, and the dosage form employed.
  • the present invention also encompasses a bactericidal, insecticidal/sputum composition having a compound of the formula (I) as an active ingredient.
  • the active ingredient in the bactericidal, insecticidal/tantalum composition is present in an amount between 0.5 and 99% by weight.
  • the bactericidal, insecticidal/sputum composition also includes agricultural, forestry, and hygienic acceptable carriers.
  • the compound of the formula (I) of the present invention When used alone, it is effective for controlling diseases, weeds, pests/cockroaches, and they can also be used together with other biochemical substances including other fungicides, insecticides/cockroaches. Agents, herbicides, plant growth regulators or fertilizers, etc., and thereby produce additional advantages and effects.
  • the preparation of the compound of the formula (I) provided by the present invention as an active ingredient can be prepared into any desired dosage form such as dry compressed granules, a flowable mixture, granules, wettable powders, water-dispersible granules, Emulsifying concentrates, powders, powder concentrates, microemulsions, suspending agents, emulsifiable concentrates, aqueous emulsions, soluble liquids, aqueous agents, dispersible liquids, suitable adjuvants including carriers (diluents) and other adjuvants Such as spreading agents, emulsifiers, wetting agents, dispersants, adhesives and decomposers.
  • These formulations contain the compound of the present invention in admixture with an inert, pharmacologically acceptable solid or liquid diluent.
  • compositions of the present invention may also be formulated into any desired dosage form such as dry compressed granules, flowable mixtures, granules, wettable powders, water-dispersible granules, emulsifiable concentrates, powders, powders.
  • Concentrates, microemulsions, suspensions, emulsifiable concentrates, aqueous emulsions, soluble liquids, aqueous agents, dispersible liquids, suitable adjuvants include carriers (diluents) and other adjuvants such as spreading agents, emulsifiers, wetting agents , dispersants, adhesives and decomposers.
  • These formulations contain the compound of the present invention in admixture with an inert, pharmacologically acceptable solid or liquid diluent.
  • the invention will be further illustrated by the use of some of the compounds listed in Tables 1 to 2 below, but is not intended to limit the invention.
  • the melting point given in the present invention is not corrected.
  • the compound of the formula (I) synthesized by the present invention is a viscous solid, some of the viscous solid refrigerators are solidified into a non-tacky solid after being placed; the compound of the formula (I) synthesized by the present invention is In the case of viscous liquids, some viscous liquids will solidify when placed in the refrigerator. All of the compounds in Table 1 were observed to have molecular ion peaks in LC-Mass (Agilent 1260/6120) and/or GC-mass (7890-5975C).
  • the compound of the formula (I) of the present invention can be obtained by the following reaction formula.
  • (III), (IV) and (V) in the reaction formula can be prepared by purchasing or according to the relevant reference methods;
  • L in the reaction formula is a leaving group such as chlorine, bromine, etc.
  • M is hydrogen, sodium or Potassium and the like, other substituents are as defined above unless otherwise specified.
  • the compound of formula (I) can be prepared by using a suitable solvent such as tetrahydrofuran, dioxane, water, ethanol, methanol, acetonitrile, dichloromethane, dichloroethane or N,N-dimethylformamide.
  • a suitable solvent such as tetrahydrofuran, dioxane, water, ethanol, methanol, acetonitrile, dichloromethane, dichloroethane or N,N-dimethylformamide.
  • the compound can be prepared by oxidation with a conventional oxidizing agent such as hydrogen peroxide, m-chloroperoxybenzoic acid, peracetic acid, hypochlorite, oxalic acid, t-butanol, potassium persulfate or sodium perborate.
  • a conventional oxidizing agent such as hydrogen peroxide, m-chloroperoxybenzoic acid, peracetic acid, hypochlorite,
  • the compound of the formula (II) can be produced by using a suitable solvent such as ethanol, methanol, tetrahydrofuran, dioxane, acetonitrile, dichloromethane, dichloroethane or N,N-dimethylformamide. Reacting with a compound of formula (IV) and a compound of formula (V) in the absence of a base or a suitable base such as potassium carbonate, sodium carbonate, triethylamine, pyridine, sodium hydride, sodium hydroxide or potassium hydroxide A compound represented by the formula (II).
  • a suitable solvent such as ethanol, methanol, tetrahydrofuran, dioxane, acetonitrile, dichloromethane, dichloroethane or N,N-dimethylformamide. Reacting with a compound of formula (IV) and a compound of formula (V) in the absence of a base or a suitable base such as potassium carbonate, sodium carbonate, tri
  • EXAMPLE 1 This example illustrates the preparation of compound 28 in Table 1.
  • N-ethyl-6-methylthio-3-nitropyridin-2-amine (Compound 28 in Table 1) N-ethyl-6-chloro-3-nitropyridin-2-amine (9 mmol), 25
  • the sodium methylthiolate solution (5 mL) and tetrahydrofuran (20 mL) were reacted to completion at 0 ° C to 50 ° C, poured into ice water, extracted with ethyl acetate, and the organic phase was washed with water, dried over anhydrous sodium sulfate and evaporated.
  • the crude product was purified by column chromatography (EtOAcEtOAcEtOAcEtOAcEtOAcEtOAcEtOAc
  • EXAMPLE 2 This example illustrates the preparation of compound 29 in Table 1.
  • N-ethyl-6-methylsulfonyl-3-nitropyridin-2-amine (Compound 29 in Table 1) N-ethyl-6-methylthio-3-nitropyridin-2-amine (4 mmol , m-chloroperoxybenzoic acid (4mmol) and dichloromethane (10mL), after reacting to complete at 0 ° C to 35 ° C, adding ice brine, liquid separation, the aqueous layer is extracted with dichloromethane, the organic phase is combined and After washing with water and dried over anhydrous sodium sulfate, the solvent was evaporated.
  • EXAMPLE 3 This example illustrates the preparation of compound 30 in Table 1.
  • N-ethyl-6-methylsulfonyl-3-nitropyridin-2-amine (Compound 30 in Table 1) N-ethyl-6-methylthio-3-nitropyridin-2-amine (4 mmol) , m-chloroperoxybenzoic acid (10 mmol) and dichloromethane (10 mL) were reacted to completion at 25 ° C to reflux temperature, iced brine was added, the organic phase was separated, and the aqueous phase was extracted with dichloromethane. After washing with water and dried over anhydrous sodium sulfate, the solvent was evaporated.
  • N-(1-phenylethyl)-6-methylthio-3-nitropyridin-2-amine (Compound 98 in Table 1) N-(1-phenylethyl)-6-chloro-3- Nitropyridin-2-amine (8mmol), 25% sodium thiomethoxide solution (5mL) and tetrahydrofuran (10mL), after reacting at 0 ° C to 50 ° C to complete, add ice brine, ethyl acetate extraction, combined organic phase The mixture was washed with water and dried over anhydrous sodium sulfate and evaporated.
  • EXAMPLE 5 This example illustrates the preparation of compound 100 in Table 1.
  • N-(1-phenylethyl)-6-methylsulfonyl-3-nitropyridin-2-amine (Compound 100 in Table 1) N-(1-phenylethyl)-6-methylthio- 3-nitropyridin-2-amine (4mmol), m-chloroperoxybenzoic acid (10mmol) and dichloromethane (10mL), reacted at 25 ° C to the reflux temperature of the system to complete, add ice brine, liquid separation, two The aqueous layer was extracted with chloromethane. EtOAc was evaporated.
  • EXAMPLE 6 This example illustrates the preparation of compound 101 in Table 1.
  • EXAMPLE 8 This example illustrates the preparation of compound 242 in Table 1.
  • N-phenylethyl-6-chloro-3-nitropyridin-2-amine 2,6-dichloro-3-nitropyridine (10 mmol)
  • potassium carbonate (10 mmol)
  • ethanol (20 mL)
  • phenethylamine The (10 mmol) ethanol solution was reacted to completion at 0 °C to 50 °C.
  • the reaction mixture was poured into EtOAc EtOAc.
  • N-phenylethyl-6-methylthio-3-nitropyridin-2-amine (Compound 242 in Table 1) N-phenylethyl-6-chloro-3-nitropyridin-2-amine ( 8mmol), 25% sodium thiomethoxide solution (5mL) and tetrahydrofuran (20mL) were reacted to complete at 0 ° C to 50 ° C, poured into ice water, extracted with ethyl acetate, and the organic phase was washed with water and anhydrous sodium sulfate After drying, the solvent was evaporated. EtOAc m.
  • N-phenylethyl-6-methylsulfoxide-3-nitropyridin-2-amine (Compound 243 in Table 1) N-phenylethyl-6-methylthio-3-nitropyridine-2 -amine (4 mmol), m-chloroperoxybenzoic acid (4 mmol) and dichloromethane (10 mL), EtOAc EtOAc (EtOAc) The combined organic phases were dried with EtOAc EtOAc m.
  • EXAMPLE 10 This example illustrates the preparation of compound 244 in Table 1.
  • N-phenylethyl-6-methylsulfonyl-3-nitropyridin-2-amine (Compound 244 in Table 1) N-phenylethyl-6-methylthio-3-nitropyridine-2- Amine (4mmol), m-chloroperoxybenzoic acid (10mmol) and dichloromethane (10mL), after reaction at 25 ° C to the reflux temperature of the system to complete, add ice brine, separate the liquid, extract the aqueous layer with dichloromethane, and combine organic The mixture was washed with water and dried over anhydrous sodium sulfate.
  • the synthesized compounds were sterilized and tested for insecticidal/sputum.
  • the results of some experiments are as follows.
  • test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and then diluted to the desired concentration with sterile water containing 0.2% Tween80 emulsifier, and a blank containing no test compound is provided.
  • a suitable solvent such as N,N-dimethylformamide (DMF)
  • sterile water containing 0.2% Tween80 emulsifier 0.2% Tween80 emulsifier
  • the culture dish is placed in a constant temperature biochemical incubator at 28 °C, and the mycelial growth diameter is measured after 4 days.
  • the EXCEL statistical software was used for analysis and the mycelial growth inhibition rate (%) was calculated.
  • the activity is divided into four grades A, B, C, and D with respect to the blank control, 100 ⁇ inhibition rate (%) ⁇ 90 is A grade, 90 > inhibition rate (%) ⁇ 70 is B grade, 70 > inhibition Rate (%) ⁇ 50 is C level, 50> inhibition rate (%) ⁇ 0 is D level.
  • the synthesized compounds were determined for phytophythora capsici, Botrytis cinerea, and Sclerotonia sclerotiorum. Bactericidal activity.
  • compounds 03, 29, 45, 54, 96, 97, 243, 246, 339, 340, 343, 1096 have Class A activity against Fusarium graminearum, compounds 30, 32, 38, 39 , 91, 333, etc.
  • compounds 03, 29, 30, 54, 171, 172, 243 have Class A activity against Phytophthora capsici, compounds 30, 32, 33, 35, 36, 38, 39, 48, 96 , 97, 100, 333, 334, 340, etc. have class B activity against Phytophthora capsici, compounds 45, 85, 89, 103, 165, 166, 244, 246, 252, 270, 279, 328, 336, 337, 339, 343, 342, 345, 1094, etc.
  • compounds 29, 30, 36, 246, 342, 345 have Class A activity against Botrytis cinerea
  • compounds 01, 28, 29, 32, 35, 38, 45, 48, 54, 89 , 96, 100, 171, 243, 252, 270, 279, 328, 343, etc. have class B activity against Botrytis cinerea
  • compounds 03, 04, 33, 39, 43, 97, 103, 280, 333, 334, 335, 337, 339, 340, 341, 495, 496, 510, 1096 have C-level activity against Botrytis cinerea; at the test concentration of 10 mg/L, compounds 01, 28, 29, 30, 35, 36, 89, etc.
  • Grade B activity against Botrytis cinerea Compounds 32, 38, 45, 96, 243, 246 have Class C activity against Botrytis cinerea; Compounds 01, 28, 29, 32, 35 at 5 mg/L test concentration , 36, 38, etc. have C-class activity against Botrytis cinerea.
  • the pathogen has class A activity, and compounds 29, 35, 39, 48, 89, 100, 103, 243, 270, 333, 342 have class B activity against Sclerotinia sclerotiorum, compounds 01, 04, 101, 166, 171, 242, 244, 252, 271, 279, 280, 334, 337, 339, 340, 344, 496 have C-class activity against Sclerotinia sclerotiorum; at 10 mg/L test concentration, compounds 30, 33, 328, etc.
  • Sclerotinia sclerotiorum has class A activity
  • compounds 29, 30, 36, 45, 333 have class B activity against Sclerotinia sclerotiorum
  • compounds 35, 38, 39, 54, 89, 100 have C grade for Sclerotinia sclerotiorum Activity
  • compounds 29, 30, 33, 328 have B-level activity against Sclerotinia sclerotiorum
  • compounds 30, 36, 38, 39, 45, 89, 333 have C against Sclerotinia sclerotiorum Grade activity
  • Compounds 29, 30, 33, etc. have class C activity against Sclerotinia sclerotiorum at a concentration of 2.5 mg/L.
  • test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and then diluted to the desired concentration with sterile water containing 0.2% Tween80 emulsifier, and a blank containing no test compound is provided.
  • a suitable solvent such as N,N-dimethylformamide (DMF)
  • sterile water containing 0.2% Tween80 emulsifier 0.2% Tween80 emulsifier
  • a blank containing no test compound is provided for the control.
  • the treatment was repeated 4 times; the Cucumber ash pathogen was transferred to the PDA plate and cultured, transferred to the PD medium, and cultured in a constant temperature water bath for 4 days; the cultured hyphae ball was pulverized with a homogenizer and formulated with water.
  • test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and then diluted to the desired concentration with sterile water containing 0.2% Tween80 emulsifier, and a blank containing no test compound is provided.
  • a suitable solvent such as N,N-dimethylformamide (DMF)
  • compounds 29, 48, 100, 243, 244, 336, 337, 339, 340, etc. have more than 90% control activity against corn rust; compounds 30, 46, 98, 253, 280, 334, 346 It has more than 80% control activity against corn rust; compounds 274, 510 have more than 70% control activity against corn rust.
  • the compounds 243, 244 and the like have more than 80% control activity against corn rust.
  • the compounds 243, 244 and the like have a control activity against corn rust of 70% or more.
  • the phenyl sulfone or its derivative represented by the formula (B), the formula (C) and the formula (D) does not have a control effect on corn rust at a dose of 100 mg/L of not more than 50%.
  • compounds 29, 30, 85, 97, 100, 244, 252, 337 and the like have more than 90% control activity against rice sheath blight; compounds 83, 97, 171, 243, 246, 270, 328 339, 343, 344, etc. have more than 80% control activity against rice sheath blight; compounds 247, 333, 334, 340, 342 have more than 70% control activity against rice sheath blight.
  • compounds 97, 252, and 244 have more than 90% control activity against rice sheath blight; 83, 85, and 243 have more than 70% control activity against rice sheath blight.
  • compound 244 has more than 90% control activity against rice sheath blight; compound 97 has more than 80% control activity against rice sheath blight; compound 83, 85, 243, 252, etc. Blight has more than 70% control activity.
  • the phenyl sulfone or its derivative represented by formula (B), formula (C) and formula (D) has a control effect against rice sheath blight at a dose of 100 mg/L of not more than 50%; formula (B), formula The phenyl sulfone or its derivative represented by (C) and formula (D) does not have a control effect against rice sheath blight at a dose of 50 mg/L of not more than 30%.
  • Example 15 Bactericidal activity against wheat white powder pathogen (Erisiphe griminis) (pot method)
  • test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and then diluted to the desired concentration with sterile water containing 0.2% Tween80 emulsifier, and a blank containing no test compound is provided.
  • a suitable solvent such as N,N-dimethylformamide (DMF)
  • For the control take the pots with a stem of about 15cm, and soak the seeds of 20 full and healthy seeds of wheat, and use them for the test after growing the leaves; take the prepared wheat seedlings with a certain concentration of spray treatment, one Inoculation of the bacteria after the day. Each treatment was repeated 3 times, and a blank containing no test compound was set as a control. After moisturizing and warming culture until the onset of the blank control, the area of the lesion was examined and the drug control effect was calculated. Activity is relative to the blank control as a percentage.
  • compounds 341 and 343 have more than 90% control effect on wheat powdery mildew; compounds 168, 246, 344, 510 have more than 80% control effect on wheat powdery mildew; compounds 247, 252, etc. Wheat powdery mildew has more than 70% control effect.
  • the phenyl sulfone or the derivative thereof represented by the formula (B), the formula (C) and the formula (D) has a control effect against wheat powdery mildew of 0% at a concentration of 500 mg/L.
  • the aphid was selected as a subject, and the activity of the compound of the present invention against aphids was measured by a dipping method.
  • Impregnation method The test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and diluted with water containing 0.2% Tween80 emulsifier to the desired concentration, and the blank containing no test compound is Control, repeated 3 times per treatment.
  • a suitable solvent such as N,N-dimethylformamide (DMF)
  • Tween80 emulsifier to the desired concentration
  • the blank containing no test compound is Control, repeated 3 times per treatment.
  • the Aphis fabae is attached to the newly-extracted bean seedlings, and each plant is connected to more than 20 heads.
  • the bean seedlings are immersed together with the test insects in the liquid of the formula (I) provided by the present invention, and taken out after 5 seconds.
  • the excess liquid was aspirated, inserted into the absorbent sponge, covered with a glass tube, and the number of surviving and dead insects was checked after 24 hours, and the results were averaged.
  • the activity was divided into four levels A, B, C, and D, and 100% ⁇ mortality (%) ⁇ 90 for grade A, 90 > mortality (%) ⁇ 70 for grade B, relative to the blank control. 70> Mortality (%) ⁇ 50 is C grade, 50 > mortality (%) ⁇ 0 is D grade.
  • the results indicate that the compounds of the present invention are active against broad bean meal, and some of the results are listed below:
  • compounds 165 and 172 have Class A activity against aphids; Compounds 46, 247, 279, 326, 341, 343, 495 have Class B activity against aphids; Compounds 52, 54, 166, 246, 332 344, 345, 494, 524, etc. have class C activity on aphids.
  • compound 172 or the like has a class B activity against aphids
  • compound 165 or the like has a class C activity on aphids.
  • the phenyl sulfone or the derivative thereof represented by the formula (B), the formula (C) and the formula (D) has a mortality rate against aphids of less than 50% at a concentration of 500 mg/L.
  • test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and then diluted with the water containing 0.2% Tween80 emulsifier to the desired concentration, and the blank containing no test compound is used as a control. , repeated 3 times for each treatment.
  • a suitable solvent such as N,N-dimethylformamide (DMF)
  • Tween80 emulsifier to the desired concentration
  • the blank containing no test compound is used as a control. , repeated 3 times for each treatment.
  • compounds 36, 39 have A-grade activity against cotton red spider; compounds 33, 345, 495, 1114 have B-grade activity against cotton red spider; compounds 168, 1096 and other cotton-red spiders have grade C active.
  • compound 345 and the like had a class C activity against cotton red spider.
  • the phenyl sulfone or the derivative thereof represented by the formula (B), the formula (C) and the formula (D) has a mortality rate of less than 15% at a concentration of 500 mg/L.

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Abstract

Disclosed are pyridine sulfone as represented in formula (I) and derivatives of pyridine sulfone, and preparation method and application of pyridine sulfone. In formula (I), n, m, R, R1, R2, R3, R4, and R5 have the definitions given in the description. Formula (I) compound in the present invention has broad spectrum biological activities such as bactericidal and/or insecticidal/mite activities, especially has activities for diseases such as rice sheath blight and corn rust.

Description

吡啶砜及其衍生物、制备方法与应用Pyridyl sulfone and its derivatives, preparation method and application 【技术领域】[Technical Field]
本发明涉及具有杀菌、杀虫/螨生物活性的吡啶砜及其衍生物以及其制备方法、含有所述化合物的杀菌、杀虫/螨剂组合物、以及用这些化合物控制有害病菌、害虫/螨的用途与方法。The present invention relates to pyridone and its derivatives having bactericidal, insecticidal/industrial activity, and a process for the preparation thereof, a bactericidal, insecticidal/sputum composition containing the same, and the use of these compounds for controlling harmful bacteria, pests/cockroaches Use and method.
【背景技术】【Background technique】
有害病菌、害虫/螨的防治在实现高效农业的过程中非常重要。同时有害病菌、害虫/螨的防治在林、牧、副、渔及公共卫生中也很重要。虽然市场上已有很多有害病菌、害虫/螨防治剂，但是由于市场的不断扩大以及外来的有害病菌、害虫/螨和它们的抗性、药物的使用寿命、药物的经济性等问题以及人们对环境、环境有益生物的日益重视，需要科学家们不断研究，进而开发出新的高效、安全、经济、环境相容和具有不同作用方式的杀菌、杀虫剂新品种。The prevention and control of harmful bacteria and pests/cockroaches is very important in the process of achieving efficient agriculture. At the same time, the control of harmful bacteria and pests/cockroaches is also important in forestry, animal husbandry, deputy, fishery and public health. Although there are many harmful pathogens and pests/sputum control agents on the market, due to the continuous expansion of the market and the problems of external harmful bacteria, pests and cockroaches and their resistance, the service life of drugs, the economics of drugs, etc. The increasing emphasis on environmental and environmental beneficial organisms requires scientists to continuously research and develop new new varieties of bactericidal and insecticides that are efficient, safe, economical, environmentally compatible and have different modes of action.
砜及其衍生物在药物化学中是一类重要化合物，它们具有广谱的生物活性，具有生物活性的砜及其衍生物的报道有很多，但吡啶砜及其衍生物的报道却不多见，即使偶见吡啶砜及其衍生物的报道，也大多是关于其医药活性的。对有害病菌和/或害虫/螨具有活性的吡啶砜及其衍生物的报道不易找到。如文献报道的具有式(A)所示的砜类化合物就属医药领域。Sulfone and its derivatives are important compounds in medicinal chemistry. They have a broad spectrum of biological activities. There are many reports on biologically active sulfones and their derivatives, but reports of pyridine sulfone and its derivatives are rare. Even the occasional reports of pyridine sulfone and its derivatives are mostly related to its medicinal activity. Reports of pyridylsulfone and its derivatives active against harmful bacteria and/or pests/caries are not easily found. The sulfone compound represented by the formula (A) as reported in the literature belongs to the field of medicine.
Figure PCTCN2018123428-appb-000001
Figure PCTCN2018123428-appb-000001
为获得对有害病菌和/或害虫/螨具有活性的新颖结构化合物，砜类化合物，特别是吡啶砜及其衍生物一直是我们研究的方向之一。通过近几年的研究，申请人发现了一类新颖结构的吡啶砜及其衍生物具有广谱生物活性。为与式(A)所示的苯基砜类化合物相比较，申请人特合成式(B)、式(C)和式(D)所示的苯基砜及其衍生物并测试了其生物活性。本发明的化合物不仅具有显著不同的结构特点，而且这些结构上的差异使得本发明的化合物具有更广谱、更优异的生物活性，有些化合物如29、244等显示出较式(B)、式(C)和式(D)所示的苯基砜及其衍生物更广谱和更高效的生物活性。Sulfone compounds, especially pyridine sulfone and its derivatives, have been one of our research directions in order to obtain novel structural compounds active against harmful bacteria and/or pests/sputums. Through recent studies, Applicants have discovered a novel class of pyridylsulfone and its derivatives with broad-spectrum biological activity. In comparison with the phenyl sulfone compound represented by the formula (A), the applicant specifically synthesizes the phenyl sulfone represented by the formula (B), the formula (C) and the formula (D) and derivatives thereof and tests the organism thereof. active. The compounds of the present invention not only have significantly different structural characteristics, but also these structural differences allow the compounds of the present invention to have a broader spectrum and superior biological activity, and some compounds such as 29, 244, etc. exhibit a formula (B), (C) and phenyl sulfone and its derivatives represented by formula (D) are more broad-spectrum and more efficient biological activities.
Figure PCTCN2018123428-appb-000002
Figure PCTCN2018123428-appb-000002
【发明内容】[Summary of the Invention]
本发明提供了式(I)所示的具有病菌、害虫/螨等生物活性的吡啶砜及其衍生物：The present invention provides a pyridyl sulfone having a biological activity such as a pathogen, a pest, or a cockroach, and a derivative thereof, represented by the formula (I):
Figure PCTCN2018123428-appb-000003
Figure PCTCN2018123428-appb-000003
其中：among them:
I.R代表硝基；I.R represents a nitro group;
II.R 1代表氢、C 1-C 12烷基或C 3-C 6环烷基； II. R 1 represents hydrogen, C 1 -C 12 alkyl or C 3 -C 6 cycloalkyl;
III.R 2代表氢、卤素、C 1-C 12烷基或C 3-C 6环烷基； III. R 2 represents hydrogen, halogen, C 1 -C 12 alkyl or C 3 -C 6 cycloalkyl;
IV.R 3代表氢、C 1-C 12烷基、C 2-C 12链烯基、C 2-C 12链炔基或苯基； IV. R 3 represents hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or phenyl;
V.R 4代表氢、C 1-C 12烷基或C 3-C 6环烷基； VR 4 represents hydrogen, C 1 -C 12 alkyl or C 3 -C 6 cycloalkyl;
VI.R 5代表氢、C 1-C 12烷基、C 3-C 8环烷基、苯基、苯基甲基、苯基乙基、噻唑基、噻唑基甲基、噻唑基乙基、呋喃基、呋喃基甲基、呋喃基乙基、噻酚基、噻酚基甲基、噻酚基乙基、四氢呋喃基、四氢呋喃基甲基、四氢呋喃基乙基、吡啶基、卤代吡啶基、吡啶基甲基、卤代吡啶基甲基、吡啶基乙基、卤代吡啶基乙基； VI. R 5 represents hydrogen, C 1 -C 12 alkyl, C 3 -C 8 cycloalkyl, phenyl, phenylmethyl, phenylethyl, thiazolyl, thiazolylmethyl, thiazolylethyl, Furanyl, furylmethyl, furylethyl, thiophenol, thiophenoxymethyl, thiophenethyl, tetrahydrofuranyl, tetrahydrofuranylmethyl, tetrahydrofuranylethyl, pyridyl, halopyridyl, Pyridylmethyl, halopyridylmethyl, pyridylethyl, halopyridylethyl;
VII.n代表0、1或2；m代表1或2；且VII.n represents 0, 1 or 2; m represents 1 or 2;
1)如在II.、III.、IV.、V.、VI.中所确定的含义，其中0个氢原子、部分氢原子或全部氢原子被选自下列中相同或不同的取代基取代：卤素、C 1-C 12烷基、C 1-C 12烷氧基、苯基、卤代苯基、C 1-C 12烷基苯基、被卤素和C 1-C 6烷基取代苯基； 1) The meaning as defined in II., III., IV., V., VI. wherein 0 hydrogen atoms, partial hydrogen atoms or all hydrogen atoms are substituted by the same or different substituents selected from the group consisting of: Halogen, C 1 -C 12 alkyl, C 1 -C 12 alkoxy, phenyl, halophenyl, C 1 -C 12 alkylphenyl, phenyl substituted by halogen and C 1 -C 6 alkyl ;
2)硝基为5-硝基时，n不代表0；2) When the nitro group is a 5-nitro group, n does not represent 0;
3)m＝1时，通式(I)化合物即通式(Ia)化合物；m＝2时，通式(I)化合物即通式(Ib)化合物；3) when m=1, the compound of the formula (I) is a compound of the formula (Ia); when m=2, the compound of the formula (I) is a compound of the formula (Ib);
Figure PCTCN2018123428-appb-000004
Figure PCTCN2018123428-appb-000004
4)通式(I)化合物不代表N-乙基-N-((2-氯噻唑-5-基)甲基)-6-甲硫基-3-硝基吡啶-2-胺和N-环丁基-6-甲硫基-3-硝基吡啶-2-胺；4) The compound of the formula (I) does not represent N-ethyl-N-((2-chlorothiazol-5-yl)methyl)-6-methylthio-3-nitropyridin-2-amine and N- Cyclobutyl-6-methylthio-3-nitropyridin-2-amine;
上面给出的化合物(I)的定义中，所用术语不论单独使用还是用在复合词中，代表如下取代基：In the definition of the compound (I) given above, the terms used, whether used alone or in a compound, represent the following substituents:
卤素：指氟、氯、溴、碘；Halogen: means fluorine, chlorine, bromine, iodine;
烷基：指直链或支链烷基；Alkyl: means a straight or branched alkyl group;
环烷基：指饱和或不饱和的环烷基；Cycloalkyl: means a saturated or unsaturated cycloalkyl group;
杂环烷基：指饱和或不饱和的杂环烷基，式中至少有1个N，O和/或S；Heterocycloalkyl: a saturated or unsaturated heterocycloalkyl group having at least one N, O and/or S;
链烯基；指直链或支链并可在任何位置上存在有双键；Alkenyl; means straight or branched and may have a double bond at any position;
链炔基；指直链或支链并可在任何位置上存在有三键。Alkynyl; means straight or branched and may have a triple bond at any position.
本发明优选的化合物为：式(I)中：Preferred compounds of the invention are: in formula (I):
I.R代表3-硝基；I.R represents 3-nitro;
II.R 1代表氢或C 1-C 12烷基； II. R 1 represents hydrogen or C 1 -C 12 alkyl;
III.R 2代表氢、卤素或C 1-C 12烷基； III. R 2 represents hydrogen, halogen or C 1 -C 12 alkyl;
IV.R 3代表氢、C 1-C 12烷基、C 2-C 12链烯基、C 2-C 12链炔基或苯基； IV. R 3 represents hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or phenyl;
V.R 4代表氢或C 1-C 12烷基； VR 4 represents hydrogen or C 1 -C 12 alkyl;
VI.R 5代表氢、C 1-C 12烷基、C 3-C 8环烷基、苯基、苯基甲基、苯基乙基、噻唑基、噻唑基甲基、噻唑基乙基、呋喃基、呋喃基甲基、呋喃基乙基、噻酚基、噻酚基甲基、噻酚基乙基、四氢呋喃基、四氢呋喃基甲基、四氢呋喃基乙基、吡啶基、卤代吡啶基、吡啶基甲基、卤代吡啶基甲基、吡啶基乙基、卤代吡啶基乙基； VI. R 5 represents hydrogen, C 1 -C 12 alkyl, C 3 -C 8 cycloalkyl, phenyl, phenylmethyl, phenylethyl, thiazolyl, thiazolylmethyl, thiazolylethyl, Furanyl, furylmethyl, furylethyl, thiophenol, thiophenoxymethyl, thiophenethyl, tetrahydrofuranyl, tetrahydrofuranylmethyl, tetrahydrofuranylethyl, pyridyl, halopyridyl, Pyridylmethyl, halopyridylmethyl, pyridylethyl, halopyridylethyl;
VII.n代表0、1或2；m代表1或2；且VII.n represents 0, 1 or 2; m represents 1 or 2;
1)如在II.、III.、IV.、V.、VI.中所确定的含义，其中0个氢原子、部分氢原子或全部氢原子被选自下列中相同或不同的取代基取代：卤素、C 1-C 12烷基、C 1-C 12烷氧基、苯基、卤代苯基、C 1-C 12烷基苯基、被卤素和C 1-C 6烷基取代苯基； 1) The meaning as defined in II., III., IV., V., VI. wherein 0 hydrogen atoms, partial hydrogen atoms or all hydrogen atoms are substituted by the same or different substituents selected from the group consisting of: Halogen, C 1 -C 12 alkyl, C 1 -C 12 alkoxy, phenyl, halophenyl, C 1 -C 12 alkylphenyl, phenyl substituted by halogen and C 1 -C 6 alkyl ;
2)硝基为5-硝基时，n不代表0；2) When the nitro group is a 5-nitro group, n does not represent 0;
3)m＝1时，通式(I)化合物即通式(Ia)化合物；m＝2时，通式(I)化合物即通式(Ib)化合物；3) when m=1, the compound of the formula (I) is a compound of the formula (Ia); when m=2, the compound of the formula (I) is a compound of the formula (Ib);
Figure PCTCN2018123428-appb-000005
Figure PCTCN2018123428-appb-000005
4)通式(I)化合物不代表N-乙基-N-((2-氯噻唑-5-基)甲基)-6-甲硫基-3-硝基吡啶-2-胺和N-环丁基-6-甲硫基-3-硝基吡啶-2-胺。4) The compound of the formula (I) does not represent N-ethyl-N-((2-chlorothiazol-5-yl)methyl)-6-methylthio-3-nitropyridin-2-amine and N- Cyclobutyl-6-methylthio-3-nitropyridin-2-amine.
本发明进一步优选的化合物为：式(I)中：Further preferred compounds of the invention are: in formula (I):
I.R代表3-硝基；I.R represents 3-nitro;
II.R 1代表氢或C 1-C 12烷基； II. R 1 represents hydrogen or C 1 -C 12 alkyl;
III.R 2代表氢、卤素或C 1-C 12烷基； III. R 2 represents hydrogen, halogen or C 1 -C 12 alkyl;
IV.R 3代表氢、C 1-C 12烷基、C 2-C 12链烯基、C 2-C 12链炔基或苯基； IV. R 3 represents hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or phenyl;
V.R 4代表氢或C 1-C 12烷基； VR 4 represents hydrogen or C 1 -C 12 alkyl;
VI.R 5代表氢、C 1-C 12烷基、C 3-C 8环烷基、苯基、苯基甲基、苯基乙基、噻唑基、噻唑基甲基、噻唑基乙基、呋喃基、呋喃基甲基、呋喃基乙基、噻酚基、噻酚基甲基、噻酚基乙基、四氢呋喃基、四氢呋喃基甲基、四氢呋喃基乙基、吡啶基、卤代吡啶基、吡啶基甲基、卤代吡啶基甲基、吡啶基乙基、卤代吡啶基乙基； VI. R 5 represents hydrogen, C 1 -C 12 alkyl, C 3 -C 8 cycloalkyl, phenyl, phenylmethyl, phenylethyl, thiazolyl, thiazolylmethyl, thiazolylethyl, Furanyl, furylmethyl, furylethyl, thiophenol, thiophenoxymethyl, thiophenethyl, tetrahydrofuranyl, tetrahydrofuranylmethyl, tetrahydrofuranylethyl, pyridyl, halopyridyl, Pyridylmethyl, halopyridylmethyl, pyridylethyl, halopyridylethyl;
VII.n代表1或2；m代表1；且VII.n represents 1 or 2; m represents 1;
1)如在II.、III.、IV.、V.、或VI.中所确定的含义，其中0个氢原子、部分氢原子或全部氢原子被选自下列中相同或不同的取代基取代：卤素、C 1-C 12烷基、C 1-C 12烷氧基、苯基、卤代苯基、C 1-C 12烷基苯基、被卤素和C 1-C 6烷基取代苯基。 1) meaning as defined in II., III., IV., V., or VI. wherein 0 hydrogen atoms, partial hydrogen atoms or all hydrogen atoms are replaced by the same or different substituents selected from the following : halogen, C 1 -C 12 alkyl, C 1 -C 12 alkoxy, phenyl, halophenyl, C 1 -C 12 alkylphenyl, substituted by halogen and C 1 -C 6 alkyl base.
本发明更进一步优选的化合物为：式(I)中：A still further preferred compound of the invention is: in formula (I):
I.R代表3-硝基；I.R represents 3-nitro;
II.R 1代表氢或C 1-C 12烷基； II. R 1 represents hydrogen or C 1 -C 12 alkyl;
III.R 2代表氢、卤素或C 1-C 12烷基； III. R 2 represents hydrogen, halogen or C 1 -C 12 alkyl;
IV.R 3代表氢、C 1-C 12烷基、C 2-C 12链烯基、C 2-C 12链炔基或苯基； IV. R 3 represents hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or phenyl;
V.R 4代表氢或C 1-C 12烷基； VR 4 represents hydrogen or C 1 -C 12 alkyl;
VI.R 5代表氢、C 1-C 12烷基、环丙基、苯基、苯基甲基、噻唑基、噻唑基甲基、呋喃基、呋喃基甲基、噻酚基、噻酚基甲基、四氢呋喃基、四氢呋喃基甲基、吡啶基、卤代吡啶基、吡啶基甲基、卤代吡啶基甲基； VI. R 5 represents hydrogen, C 1 -C 12 alkyl, cyclopropyl, phenyl, phenylmethyl, thiazolyl, thiazolylmethyl, furyl, furylmethyl, thiophenol, thiophenol Methyl, tetrahydrofuranyl, tetrahydrofuranylmethyl, pyridyl, halopyridyl, pyridylmethyl, halopyridylmethyl;
VII.n代表1或2；m代表1；且VII.n represents 1 or 2; m represents 1;
1)如在II.、III.、IV.、V.、或VI.中所确定的含义，其中苯基上氢原子的0个、部分或全部被选自下列中相同或不同的取代基取代：卤素、C 1-C 12烷基、C 1-C 12烷氧基、苯基、卤代苯基、C 1-C 12烷基苯基、被卤素和C 1-C 6烷基取代苯基。 1) The meaning as defined in II., III., IV., V., or VI. wherein 0, part or all of the hydrogen atom on the phenyl group is substituted with the same or different substituent selected from the following : halogen, C 1 -C 12 alkyl, C 1 -C 12 alkoxy, phenyl, halophenyl, C 1 -C 12 alkylphenyl, substituted by halogen and C 1 -C 6 alkyl base.
本发明优选的式(I)化合物是：Preferred compounds of formula (I) according to the invention are:
N-甲基-6-甲砜基-3-硝基吡啶-2-胺(03)；N-methyl-6-methylsulfonyl-3-nitropyridin-2-amine (03);
N-乙基-6-甲硫基-3-硝基吡啶-2-胺(28)；N-ethyl-6-methylthio-3-nitropyridin-2-amine (28);
N-乙基-6-甲亚砜基-3-硝基吡啶-2-胺(29)；N-ethyl-6-methylsulfoxide-3-nitropyridin-2-amine (29);
N-乙基-6-甲砜基-3-硝基吡啶-2-胺(30)；N-ethyl-6-methylsulfonyl-3-nitropyridin-2-amine (30);
N-甲氧乙基-6-甲亚砜基-3-硝基吡啶-2-胺(32)；N-methoxyethyl-6-methylsulfoxide-3-nitropyridin-2-amine (32);
N-甲氧乙基-6-甲砜基-3-硝基吡啶-2-胺(33)；N-methoxyethyl-6-methylsulfonyl-3-nitropyridin-2-amine (33);
N-乙氧乙基-6-甲亚砜基-3-硝基吡啶-2-胺(35)；N-ethoxyethyl-6-methylsulfoxide-3-nitropyridin-2-amine (35);
N-乙氧乙基-6-甲砜基-3-硝基吡啶-2-胺(36)；N-ethoxyethyl-6-methylsulfonyl-3-nitropyridin-2-amine (36);
N-(3-甲氧基丙基)-6-甲亚砜基-3-硝基吡啶-2-胺(38)；N-(3-methoxypropyl)-6-methylsulfoxide-3-nitropyridin-2-amine (38);
N-(3-甲氧基丙基)-6-甲砜基-3-硝基吡啶-2-胺(39)；N-(3-methoxypropyl)-6-methylsulfonyl-3-nitropyridin-2-amine (39);
N-异丙基-6-甲砜基-3-硝基吡啶-2-胺(45)；N-isopropyl-6-methylsulfonyl-3-nitropyridin-2-amine (45);
N-丙基-6-甲硫基-3-硝基吡啶-2-胺(46)；N-propyl-6-methylthio-3-nitropyridin-2-amine (46);
N-丙基-6-甲砜基-3-硝基吡啶-2-胺(48)；N-propyl-6-methylsulfonyl-3-nitropyridin-2-amine (48);
N-正丁基-6-甲砜基-3-硝基吡啶-2-胺(54)；N-n-butyl-6-methylsulfonyl-3-nitropyridin-2-amine (54);
N-(四氢呋喃-3-基)甲基-6-甲硫基-3-硝基吡啶-2-胺(83)；N-(tetrahydrofuran-3-yl)methyl-6-methylthio-3-nitropyridin-2-amine (83);
N-(四氢呋喃-3-基)甲基-6-甲砜基-3-硝基吡啶-2-胺(85)；N-(tetrahydrofuran-3-yl)methyl-6-methylsulfonyl-3-nitropyridin-2-amine (85);
N-(四氢呋喃-2-基)甲基-6-甲砜基-3-硝基吡啶-2-胺(91)；N-(tetrahydrofuran-2-yl)methyl-6-methylsulfonyl-3-nitropyridin-2-amine (91);
N-苯基甲基-6-甲亚砜基-3-硝基吡啶-2-胺(96)；N-phenylmethyl-6-methylsulfoxide-3-nitropyridin-2-amine (96);
N-苯基甲基-6-甲砜基-3-硝基吡啶-2-胺(97)；N-phenylmethyl-6-methylsulfonyl-3-nitropyridin-2-amine (97);
N-(1-苯基乙基)-6-甲砜基-3-硝基吡啶-2-胺(100)；N-(1-phenylethyl)-6-methylsulfonyl-3-nitropyridin-2-amine (100);
N-(2-氯噻唑-5-基)甲基-6-甲亚砜基-3-硝基吡啶-2-胺(165)；N-(2-chlorothiazol-5-yl)methyl-6-methylsulfoxide-3-nitropyridin-2-amine (165);
N-(2-苯基-4-甲基噻唑-5-基)甲基-6-甲亚砜基-3-硝基吡啶-2-胺(171)；N-(2-phenyl-4-methylthiazol-5-yl)methyl-6-methylsulfoxide-3-nitropyridin-2-amine (171);
N-(2-苯基-4-甲基噻唑-5-基)甲基-6-甲砜基-3-硝基吡啶-2-胺(172)；N-(2-phenyl-4-methylthiazol-5-yl)methyl-6-methylsulfonyl-3-nitropyridin-2-amine (172);
N-苯基乙基-6-甲亚砜基-3-硝基吡啶-2-胺(243)；N-phenylethyl-6-methylsulfoxide-3-nitropyridin-2-amine (243);
N-苯基乙基-6-甲砜基-3-硝基吡啶-2-胺(244)；N-phenylethyl-6-methylsulfonyl-3-nitropyridin-2-amine (244);
N-(2-氯苯基)乙基-6-甲亚砜基-3-硝基吡啶-2-胺(246)；N-(2-chlorophenyl)ethyl-6-methylsulfoxide-3-nitropyridin-2-amine (246);
N-(2-氯苯基)乙基-6-甲砜基-3-硝基吡啶-2-胺(247)；N-(2-chlorophenyl)ethyl-6-methylsulfonyl-3-nitropyridin-2-amine (247);
N-(4-氯苯基)乙基-6-甲亚砜基-3-硝基吡啶-2-胺(252)；N-(4-chlorophenyl)ethyl-6-methylsulfoxide-3-nitropyridin-2-amine (252);
N-(4-甲基苯基)乙基-6-甲亚砜基-3-硝基吡啶-2-胺(270)；N-(4-methylphenyl)ethyl-6-methylsulfoxide-3-nitropyridin-2-amine (270);
N-(4-甲氧基苯基)乙基-6-甲亚砜基-3-硝基吡啶-2-胺(279)；N-(4-methoxyphenyl)ethyl-6-methylsulfoxide-3-nitropyridin-2-amine (279);
N-乙基-6-乙砜基-3-硝基吡啶-2-胺(328)；N-ethyl-6-ethylsulfonyl-3-nitropyridin-2-amine (328);
N-乙基-6-异丙亚砜基-3-硝基吡啶-2-胺(336)；N-ethyl-6-isopropylsulfoxide-3-nitropyridin-2-amine (336);
N-乙基-6-异丙砜基-3-硝基吡啶-2-胺(337)；N-ethyl-6-isopropylsulfonyl-3-nitropyridin-2-amine (337);
N-乙基-6-丁亚砜基-3-硝基吡啶-2-胺(339)；N-ethyl-6-butylsulfoxide-3-nitropyridin-2-amine (339);
N-乙基-6-丁砜基-3-硝基吡啶-2-胺(340)；N-ethyl-6-butsulfonyl-3-nitropyridin-2-amine (340);
N-乙基-6-烯丙硫基-3-硝基吡啶-2-胺(341)；N-ethyl-6-allylthio-3-nitropyridin-2-amine (341);
N-乙基-6-烯丙亚砜基-3-硝基吡啶-2-胺(342)；N-ethyl-6-allylsulfonyl-3-nitropyridin-2-amine (342);
N-乙基-6-烯丙砜基-3-硝基吡啶-2-胺(343)；N-ethyl-6-allylsulfonyl-3-nitropyridin-2-amine (343);
N-乙基-6-炔丙硫基-3-硝基吡啶-2-胺(344)；N-ethyl-6-propargylthio-3-nitropyridin-2-amine (344);
N-乙基-6-炔丙亚砜基-3-硝基吡啶-2-胺(345)；N-ethyl-6-propargyl sulfoxide-3-nitropyridin-2-amine (345);
N-乙基-6-苯基甲亚砜基-3-硝基吡啶-2-胺(495)；N-ethyl-6-phenylmethanesulfonyl-3-nitropyridin-2-amine (495);
N-乙基-6-((氯(苯基)甲基)亚砜基)-3-硝基吡啶-2-胺(510)；N-ethyl-6-((chloro(phenyl)methyl)sulfoxide)-3-nitropyridin-2-amine (510);
N-环丙基-6-甲砜基-3-硝基吡啶-2-胺(1096)；N-cyclopropyl-6-methylsulfonyl-3-nitropyridin-2-amine (1096);
N1,N2-双(6-甲砜基-3-硝基吡啶-2-基)乙烷-1,2-二胺(1114)。N1,N2-bis(6-methylsulfonyl-3-nitropyridin-2-yl)ethane-1,2-diamine (1114).
本发明的化合物可以一种或多种异构体的形式存在。异构体包括对映异构体、非对映异构体、几何异构体。如本发明的式(I)所示的化合物，由于其中的碳—碳双键连接不同的取代基而可以形成几何异构体(分别以Z和E来表示不同的构型)，本发明包括Z型异构体和E型异构体以及它们任何比例的混合物。本发明式(I)所示的化合物，由于其中的一个碳原子上连接四个不同的取代基而形成立体异构体(分别以R和S来表示不同的构型)，本发明包括R型异构体和S型异构体以及它们任何比例的混合物。The compounds of the invention may exist in the form of one or more isomers. Isomers include enantiomers, diastereomers, geometric isomers. A compound represented by the formula (I) of the present invention may form a geometric isomer (a different configuration is represented by Z and E, respectively) because a carbon-carbon double bond is bonded to a different substituent, and the present invention includes Z-isomers and E-isomers and mixtures thereof in any ratio. The compound of the formula (I) of the present invention, since one of the carbon atoms is bonded to four different substituents to form a stereoisomer (representing different configurations by R and S, respectively), the present invention includes the R form. Isomers and S isomers and mixtures thereof in any ratio.
虽然本发明通式(I)化合物与现有技术中公开的某些化合物都属于吡啶砜及其衍生物，但与现有技术相比，它们具有显著不同的结构特征和合成方法。并且这些结构特征的不同使得本发明的化合物具有更广谱、更优异的生物活性。Although the compounds of the general formula (I) of the present invention and certain compounds disclosed in the prior art belong to pyridyl sulfone and its derivatives, they have significantly different structural features and synthetic methods compared to the prior art. And the difference in these structural features allows the compounds of the present invention to have a broader spectrum and superior biological activity.
通式(I)化合物对农业或其他领域中的多种病菌显示出优异的活性，部分化合物对杂草或害虫/螨也显示出好的活性。因此，本发明的技术方案还包括通式(I)化合物在农业或其他领域中用作制备杀菌剂、杀虫/螨剂的用途。The compound of the formula (I) exhibits excellent activity against various pathogens in agriculture or other fields, and some compounds also exhibit good activity against weeds or pests/cockroaches. Accordingly, the technical solution of the present invention also includes the use of the compound of the general formula (I) as a bactericide, insecticide/caries agent in agriculture or other fields.
本发明还涉及一种防治有害病菌、害虫/螨的含有生物有效量的式(I)化合物和至少一种另外的选自表面活性剂、固体稀释剂和液体稀释剂的组合物。The invention further relates to a biologically effective amount of a compound of formula (I) and at least one additional composition selected from the group consisting of surfactants, solid diluents and liquid diluents for controlling harmful bacteria, pests/caries.
本发明还涉及一种防治有害病菌、害虫/螨的含有生物有效量的式(I)化合物和有效量的至少一种另外的生物活性化合物或制剂的组合物。The invention further relates to a composition comprising a biologically effective amount of a compound of formula (I) and an effective amount of at least one additional biologically active compound or formulation for controlling harmful bacteria, pests/caries.
本发明还涉及一种防治有害病菌、害虫/螨的方法，包括将生物有效量的式(I)化合物接触有害病菌、害虫/螨或其环境。同时也涉及这样一种有害病菌、害虫/螨防治方法，有害病菌、害虫/螨或其环境用生物有效量的式(I)化合物或含有式(I)化合物和生物有效量的至少一种另外的化合物或制剂的混合物进行接触来防治有害病菌、害虫/螨。The invention also relates to a method of controlling harmful germs, pests, pests, comprising contacting a biologically effective amount of a compound of formula (I) with a harmful pathogen, pest/sputum or its environment. Also relates to such a harmful pathogen, pest/clam control method, harmful bacteria, pests/sputum or its environmentally effective amount of a compound of formula (I) or a compound containing formula (I) and a biologically effective amount of at least one additional The compound or mixture of preparations is contacted to control harmful bacteria, pests/caries.
本发明的式(I)化合物在15～5000克有效成分/公顷用量下具有广谱活性：有的化合物可用于防治有害病菌，还可用于防治有害虫/螨；而且有的化合物对某些靶标具有很高的生物活性，使得在很低的剂量下就可以获得很好的效果。The compound of the formula (I) of the present invention has a broad spectrum activity at an amount of from 15 to 5000 g of active ingredient per hectare: some compounds can be used for controlling harmful bacteria, and can also be used for controlling pests/cockroaches; and some compounds for certain targets It has a high biological activity, so that good results can be obtained at very low doses.
本发明优选的组合物是含有上述优选化合物的组合物。优选的方法是使用上述优选化合物的方法。Preferred compositions of the invention are compositions containing the preferred compounds described above. A preferred method is the method using the above preferred compounds.
本发明提供的式(I)化合物，具有生物活性且有的化合物具有很好的生物活性.特别是在农业、园艺、花卉和卫生有害病菌、害虫/螨的防治方面表现出活性。这里所述的有害 生物包括，但不仅限于此，也绝不限定本发明。The compound of the formula (I) provided by the present invention has biological activity and some compounds have good biological activity, and particularly exhibits activity in the control of agricultural, horticultural, flower and hygienic harmful bacteria and pests/cockroaches. The pests described herein include, but are not limited to, the invention.
有害病菌：Harmful bacteria:
卵菌纲病害，如霜霉病、白锈菌、猝倒病、绵腐病、疫病、晚疫病等；Oomycetes diseases, such as downy mildew, white rust, squatting, cotton rot, blight, late blight, etc.;
半知菌病害，如枯萎病、根腐病、立枯病、炭疽病、黄萎病、黑星病、灰霉病、褐斑病、黑斑病、斑枯病、早疫病、轮纹病、叶枯病、茎基腐病等；Semi-bacterial diseases such as blight, root rot, blight, anthracnose, verticillium, scab, gray mold, brown spot, black spot, spot blight, early blight, round disease , leaf blight, stem-based rot, etc.;
担子菌病害，如锈病、黑穗病等；Basidiomycosis diseases such as rust and smut;
子囊菌病害，如白粉病、菌核病(亚麻菌核病、油菜菌核病、大豆菌核病、花生菌核病、烟草菌核病、辣椒菌核病、茄子菌核病、菜豆菌核病、豌豆菌核病、黄瓜菌核病、苦瓜菌核病、冬瓜菌核病、西瓜菌核病、芹菜菌核病)、黑星病等。Ascomycetes, such as powdery mildew, sclerotinia sclerotiorum (flax sclerotium, rapeseed sclerotium, soybean sclerotium, peanut sclerotium, tobacco sclerotium, capsicum sclerotium, eggplant sclerotium, bean sclerotium Disease, pea sclerotium disease, cucumber sclerotium disease, bitter gourd sclerotium disease, melon sclerotium disease, watermelon sclerotium disease, celery sclerotium disease, and scab.
有害昆虫：Harmful insects:
直翅目如蜚蠊，缨翅目如棉蓟马、稻蓟马、瓜蓟马，同翅目如叶蝉、飞虱、蚜虫，鳞翅目如东方粘虫、斜纹夜蛾、小菜蛾、甜菜夜蛾、粉纹夜蛾，菜青虫，膜翅目如叶蜂幼虫，双翅目如伊蚊、库蚊、蝇；蜱螨目如桔全爪螨、棉叶螨、二点叶螨；Orthoptera is like a scorpion, such as cotton scorpion horse, rice scorpion horse, melon scorpion horse, Homoptera such as spider mites, locusts, locusts, lepidoptera such as oriental armyworm, Spodoptera litura, Plutella xylostella, Beet armyworm, Spodoptera litura, Pieris rapae, Hymenoptera such as leaf bee larvae, Diptera such as Aedes aegypti, Culex pipiens, flies; 蜱螨目 such as orange full claw 螨, cotton leaf 螨, two-leaf 螨;
有害杂草：Harmful weeds:
单子叶杂草，如马唐、稗草、狗尾草、硬草、菵草、雀麦、看麦娘、节节麦、碱茅、星星草、野燕麦、黑麦草、匍匐翦股颖、早熟禾；Monocotyledonous weeds, such as crabgrass, valerian, foxtail, hard grass, valerian, bromegrass, maiden, wheat, alkali, star grass, wild oats, ryegrass, bentgrass, bluegrass ;
双子叶杂草，如苘麻、繁缕、龙葵、藜、凹头苋、反枝苋、洋甘菊等。Dicotyledonous weeds, such as castor, sorghum, longan, scorpion, scorpion, scorpion, chamomile, etc.
特别地，本发明式(I)化合物对水稻纹枯病、玉米锈病、黄瓜灰霉病等具有很好的活性，在较低剂量下仍具有很好的防治效果。In particular, the compound of the formula (I) of the present invention has excellent activity against rice sheath blight, corn rust, cucumber gray mold, and the like, and has a good control effect at a lower dose.
由于其积极的特性，上述化合物可有利地用于保护农业和园艺业重要的作物、家畜和种畜，以及人类常去的环境免于病菌、害虫/螨的伤害。Due to its positive properties, the above compounds can be advantageously used to protect crops, livestock and stocks that are important in agriculture and horticulture, as well as the environment in which humans often go, from the damage of germs, pests and mites.
为获得理想效果，化合物的用量因各种因素而改变，例如所用化合物、预保护物、有害生物的类型、感染程度、气候条件、施药方法、采用的剂型。To achieve the desired effect, the amount of the compound varies depending on various factors such as the compound used, the preprotectant, the type of the pest, the degree of infection, the climatic conditions, the method of administration, and the dosage form employed.
本发明还包括以通式(I)化合物作为活性组分的杀菌、杀虫/螨组合物。该杀菌、杀虫/螨组合物中活性组分的重量百分含量在0.5-99％之间。该杀菌、杀虫/螨组合物中还包括农业、林业、卫生上可接受的载体。The present invention also encompasses a bactericidal, insecticidal/sputum composition having a compound of the formula (I) as an active ingredient. The active ingredient in the bactericidal, insecticidal/tantalum composition is present in an amount between 0.5 and 99% by weight. The bactericidal, insecticidal/sputum composition also includes agricultural, forestry, and hygienic acceptable carriers.
单独使用本发明的式(I)化合物时，对控制病害、杂草、害虫/螨是有效的，它们也可以与其他生物化学物质一起使用，这些生物化学物质包括其它杀菌剂、杀虫/螨剂、除草剂、植物生长调节剂或肥料等，并由此可产生附加的优点和效果。When the compound of the formula (I) of the present invention is used alone, it is effective for controlling diseases, weeds, pests/cockroaches, and they can also be used together with other biochemical substances including other fungicides, insecticides/cockroaches. Agents, herbicides, plant growth regulators or fertilizers, etc., and thereby produce additional advantages and effects.
以本发明提供的式(I)化合物，作为有效成份的制剂，可以制成所希望的任何一种剂型如干的压缩颗粒、易流动混合剂、粒剂、可湿性粉剂、水分散粒剂、可乳化的浓缩物、 粉剂、粉状浓缩物、微乳胶、悬浮剂、乳油、水乳剂、可溶性液剂、水剂、可分散液剂，适宜的助剂包括载体(稀释剂)和其它辅助剂如展着剂、乳化剂、湿润剂、分散剂、粘着剂和分解剂。这些制剂中含有同惰性的、药理学可接受的固体或液体稀释剂混合了本发明的化合物。The preparation of the compound of the formula (I) provided by the present invention as an active ingredient can be prepared into any desired dosage form such as dry compressed granules, a flowable mixture, granules, wettable powders, water-dispersible granules, Emulsifying concentrates, powders, powder concentrates, microemulsions, suspending agents, emulsifiable concentrates, aqueous emulsions, soluble liquids, aqueous agents, dispersible liquids, suitable adjuvants including carriers (diluents) and other adjuvants Such as spreading agents, emulsifiers, wetting agents, dispersants, adhesives and decomposers. These formulations contain the compound of the present invention in admixture with an inert, pharmacologically acceptable solid or liquid diluent.
本发明的组合物实例也可以制成所希望的任何一种剂型如干的压缩颗粒、易流动混合剂、粒剂、可湿性粉剂、水分散粒剂、可乳化的浓缩物、粉剂、粉状浓缩物、微乳胶、悬浮剂、乳油、水乳剂、可溶性液剂、水剂、可分散液剂，适宜的助剂包括载体(稀释剂)和其它辅助剂如展着剂、乳化剂、湿润剂、分散剂、粘着剂和分解剂。这些制剂中含有同惰性的、药理学可接受的固体或液体稀释剂混合了本发明的化合物。Examples of the compositions of the present invention may also be formulated into any desired dosage form such as dry compressed granules, flowable mixtures, granules, wettable powders, water-dispersible granules, emulsifiable concentrates, powders, powders. Concentrates, microemulsions, suspensions, emulsifiable concentrates, aqueous emulsions, soluble liquids, aqueous agents, dispersible liquids, suitable adjuvants include carriers (diluents) and other adjuvants such as spreading agents, emulsifiers, wetting agents , dispersants, adhesives and decomposers. These formulations contain the compound of the present invention in admixture with an inert, pharmacologically acceptable solid or liquid diluent.
应明确的是，在本发明的权利要求所限定的范围内，可进行各种变换和改动。It is to be understood that various modifications and changes can be made within the scope of the appended claims.
下面用表1～表2中列出的部分化合物来进一步说明本发明，但并不限定本发明。本发明中所给熔点均未经校正，本发明所合成的式(I)化合物为粘性固体时，有些粘性固体冰箱放置后会固化为非粘性固体；本发明所合成的式(I)化合物为粘性液体时，有些粘性液体冰箱放置后会固化。表1中所有化合物在LC-Mass(Agilent 1260/6120)和/或GC-mass(7890-5975C)中均可观察到其分子离子峰。表1中所有化合物的 1H NMR(Varian INOVA-300 spectrometer)，以tetramethylsilane(TMS)作内标，氘代氯仿(CDCl 3)或氘代二甲基亚砜(DMSO)作溶剂。 The invention will be further illustrated by the use of some of the compounds listed in Tables 1 to 2 below, but is not intended to limit the invention. The melting point given in the present invention is not corrected. When the compound of the formula (I) synthesized by the present invention is a viscous solid, some of the viscous solid refrigerators are solidified into a non-tacky solid after being placed; the compound of the formula (I) synthesized by the present invention is In the case of viscous liquids, some viscous liquids will solidify when placed in the refrigerator. All of the compounds in Table 1 were observed to have molecular ion peaks in LC-Mass (Agilent 1260/6120) and/or GC-mass (7890-5975C). 1 H NMR (Varian INOVA-300 spectrometer) of all the compounds in Table 1, using tetramethylsilane (TMS) as an internal standard, deuterated chloroform (CDCl 3 ) or deuterated dimethyl sulfoxide (DMSO) as a solvent.
表1Table 1
Figure PCTCN2018123428-appb-000006
Figure PCTCN2018123428-appb-000006
Figure PCTCN2018123428-appb-000007
Figure PCTCN2018123428-appb-000007
Figure PCTCN2018123428-appb-000008
Figure PCTCN2018123428-appb-000008
Figure PCTCN2018123428-appb-000009
Figure PCTCN2018123428-appb-000009
Figure PCTCN2018123428-appb-000010
Figure PCTCN2018123428-appb-000010
Figure PCTCN2018123428-appb-000011
Figure PCTCN2018123428-appb-000011
Figure PCTCN2018123428-appb-000012
Figure PCTCN2018123428-appb-000012
Figure PCTCN2018123428-appb-000013
Figure PCTCN2018123428-appb-000013
Figure PCTCN2018123428-appb-000014
Figure PCTCN2018123428-appb-000014
Figure PCTCN2018123428-appb-000015
Figure PCTCN2018123428-appb-000015
Figure PCTCN2018123428-appb-000016
Figure PCTCN2018123428-appb-000016
Figure PCTCN2018123428-appb-000017
Figure PCTCN2018123428-appb-000017
Figure PCTCN2018123428-appb-000018
Figure PCTCN2018123428-appb-000018
Figure PCTCN2018123428-appb-000019
Figure PCTCN2018123428-appb-000019
Figure PCTCN2018123428-appb-000020
Figure PCTCN2018123428-appb-000020
Figure PCTCN2018123428-appb-000021
Figure PCTCN2018123428-appb-000021
Figure PCTCN2018123428-appb-000022
Figure PCTCN2018123428-appb-000022
Figure PCTCN2018123428-appb-000023
Figure PCTCN2018123428-appb-000023
Figure PCTCN2018123428-appb-000024
Figure PCTCN2018123428-appb-000024
Figure PCTCN2018123428-appb-000025
Figure PCTCN2018123428-appb-000025
Figure PCTCN2018123428-appb-000026
Figure PCTCN2018123428-appb-000026
Figure PCTCN2018123428-appb-000027
Figure PCTCN2018123428-appb-000027
Figure PCTCN2018123428-appb-000028
Figure PCTCN2018123428-appb-000028
Figure PCTCN2018123428-appb-000029
Figure PCTCN2018123428-appb-000029
Figure PCTCN2018123428-appb-000030
Figure PCTCN2018123428-appb-000030
Figure PCTCN2018123428-appb-000031
Figure PCTCN2018123428-appb-000031
Figure PCTCN2018123428-appb-000032
Figure PCTCN2018123428-appb-000032
Figure PCTCN2018123428-appb-000033
Figure PCTCN2018123428-appb-000033
Figure PCTCN2018123428-appb-000034
Figure PCTCN2018123428-appb-000034
Figure PCTCN2018123428-appb-000035
Figure PCTCN2018123428-appb-000035
Figure PCTCN2018123428-appb-000036
Figure PCTCN2018123428-appb-000036
Figure PCTCN2018123428-appb-000037
Figure PCTCN2018123428-appb-000037
Figure PCTCN2018123428-appb-000038
Figure PCTCN2018123428-appb-000038
Figure PCTCN2018123428-appb-000039
Figure PCTCN2018123428-appb-000039
表2Table 2
Figure PCTCN2018123428-appb-000040
Figure PCTCN2018123428-appb-000040
Figure PCTCN2018123428-appb-000041
Figure PCTCN2018123428-appb-000041
Figure PCTCN2018123428-appb-000042
Figure PCTCN2018123428-appb-000042
Figure PCTCN2018123428-appb-000043
Figure PCTCN2018123428-appb-000043
Figure PCTCN2018123428-appb-000044
Figure PCTCN2018123428-appb-000044
Figure PCTCN2018123428-appb-000045
Figure PCTCN2018123428-appb-000045
本发明式(I)所示的化合物可以通过下面所示的反应式得到。反应式中的(III)、(IV)和(V)可以通过购买或按相关参考文献方法制备得到；反应式中的L为离去基团，如氯、溴等，M为氢、钠或钾等，其它取代基除特别指明外均如前所限定。The compound of the formula (I) of the present invention can be obtained by the following reaction formula. (III), (IV) and (V) in the reaction formula can be prepared by purchasing or according to the relevant reference methods; L in the reaction formula is a leaving group such as chlorine, bromine, etc., M is hydrogen, sodium or Potassium and the like, other substituents are as defined above unless otherwise specified.
反应式1Reaction formula 1
Figure PCTCN2018123428-appb-000046
Figure PCTCN2018123428-appb-000046
反应式2Reaction formula 2
Figure PCTCN2018123428-appb-000047
Figure PCTCN2018123428-appb-000047
式(I)的化合物可以这样来制备：在合适的溶剂如四氢呋喃、二氧六环、水、乙醇、甲醇、乙腈、二氯甲烷、二氯乙烷或N,N-二甲基甲酰胺中，于-10℃～体系回流温度，式(II)所示的化合物和式(III)所示的化合物反应，得式(I n＝0)所示的化合物；在合适的溶剂如二氯甲烷、二氯乙烷、四氢呋喃、二氧六环、水、乙醇、甲醇、乙腈或N,N-二甲基甲酰胺中，于-10℃～体系回流温度，式(I n＝0)所示的化合物经常规氧化剂如过氧化氢、间氯过氧苯甲酸、过氧乙酸、次氯酸盐、草酸、过氧叔丁醇、过硫酸氢钾或过硼酸钠等氧化，即可制得式(I n＝1,2)所示的化合物。The compound of formula (I) can be prepared by using a suitable solvent such as tetrahydrofuran, dioxane, water, ethanol, methanol, acetonitrile, dichloromethane, dichloroethane or N,N-dimethylformamide. The compound represented by the formula (II) and the compound of the formula (III) are reacted at -10 ° C to the reflux temperature of the system to obtain a compound of the formula (I n = 0); in a suitable solvent such as dichloromethane , in dichloroethane, tetrahydrofuran, dioxane, water, ethanol, methanol, acetonitrile or N,N-dimethylformamide, at -10 ° C ~ system reflux temperature, the formula (I n = 0) The compound can be prepared by oxidation with a conventional oxidizing agent such as hydrogen peroxide, m-chloroperoxybenzoic acid, peracetic acid, hypochlorite, oxalic acid, t-butanol, potassium persulfate or sodium perborate. (I n = 1, 2) the compound shown.
式(II)的化合物可以这样来制备：在合适的溶剂如乙醇、甲醇、四氢呋喃、二氧六环、乙腈、二氯甲烷、二氯乙烷或N,N-二甲基甲酰胺中，在没有碱或合适碱如碳酸钾、碳酸钠、三乙胺、吡啶、氢化钠、氢氧化钠或氢氧化钾存在下，用式(IV)所示的化合物和式(V)所示的化合物反应，得式(II)所示的化合物。The compound of the formula (II) can be produced by using a suitable solvent such as ethanol, methanol, tetrahydrofuran, dioxane, acetonitrile, dichloromethane, dichloroethane or N,N-dimethylformamide. Reacting with a compound of formula (IV) and a compound of formula (V) in the absence of a base or a suitable base such as potassium carbonate, sodium carbonate, triethylamine, pyridine, sodium hydride, sodium hydroxide or potassium hydroxide A compound represented by the formula (II).
具体合成方法在下面的实施例中有更详细的阐述。Specific synthetic methods are set forth in more detail in the examples below.
以下结合实施例对本发明作进一步说明，但本发明绝非仅限于这些实施例，实施例中的收率均未经优化。The present invention is further illustrated by the following examples, but the present invention is by no means limited to these examples, and the yields in the examples are not optimized.
【具体实施方式】【Detailed ways】
合成实施例Synthesis example
实施例1 本实施例说明表1中化合物28的制备方法EXAMPLE 1 This example illustrates the preparation of compound 28 in Table 1.
Figure PCTCN2018123428-appb-000048
Figure PCTCN2018123428-appb-000048
N-乙基-6-氯-3-硝基吡啶-2-胺2,6-二氯-3-硝基吡啶(10mmol)，碳酸钾(10mmol)、乙醇(20mL)与乙胺(10mmol)的乙醇溶液于0℃至50℃反应至完全。反应混合物倒入冰盐水中，乙酸乙酯萃取，有机层经水洗后，无水硫酸钠干燥，脱除溶剂，得标题物粗产品1.85g，不经纯化，直接用于下一步合成。N-Ethyl-6-chloro-3-nitropyridin-2-amine 2,6-dichloro-3-nitropyridine (10 mmol), potassium carbonate (10 mmol), ethanol (20 mL) and ethylamine (10 mmol) The ethanol solution is reacted to completion at 0 ° C to 50 ° C. The reaction mixture was poured into EtOAc (EtOAc)EtOAc.
N-乙基-6-甲硫基-3-硝基吡啶-2-胺(表1中化合物28)N-乙基-6-氯-3-硝基吡啶-2-胺(9mmol)，25％甲硫醇钠溶液(5mL)和四氢呋喃(20mL)于0℃至50℃反应至完全后，倒入冰水中，乙酸乙酯萃取，有机相经水洗，无水硫酸钠干燥，脱除溶剂，得粗产品经柱层析(石油醚+乙酸乙酯为洗脱剂)提纯，得标题物1.35g。N-ethyl-6-methylthio-3-nitropyridin-2-amine (Compound 28 in Table 1) N-ethyl-6-chloro-3-nitropyridin-2-amine (9 mmol), 25 The sodium methylthiolate solution (5 mL) and tetrahydrofuran (20 mL) were reacted to completion at 0 ° C to 50 ° C, poured into ice water, extracted with ethyl acetate, and the organic phase was washed with water, dried over anhydrous sodium sulfate and evaporated. The crude product was purified by column chromatography (EtOAcEtOAcEtOAcEtOAc
实施例2 本实施例说明表1中化合物29的制备方法EXAMPLE 2 This example illustrates the preparation of compound 29 in Table 1.
Figure PCTCN2018123428-appb-000049
Figure PCTCN2018123428-appb-000049
N-乙基-6-甲亚砜基-3-硝基吡啶-2-胺(表1中化合物29)N-乙基-6-甲硫基-3-硝基吡啶-2-胺(4mmol)，间氯过氧化苯甲酸(4mmol)和二氯甲烷(10mL)，于0℃至35℃反应至完全后，加冰盐水，分液，水层经二氯甲烷萃取，合并有机相并经水洗和无水硫酸钠干燥，脱除溶剂，粗产品经柱层析(石油醚+乙酸乙酯为洗脱剂)提纯，得标题物0.50g。N-ethyl-6-methylsulfonyl-3-nitropyridin-2-amine (Compound 29 in Table 1) N-ethyl-6-methylthio-3-nitropyridin-2-amine (4 mmol , m-chloroperoxybenzoic acid (4mmol) and dichloromethane (10mL), after reacting to complete at 0 ° C to 35 ° C, adding ice brine, liquid separation, the aqueous layer is extracted with dichloromethane, the organic phase is combined and After washing with water and dried over anhydrous sodium sulfate, the solvent was evaporated.
实施例3 本实施例说明表1中化合物30的制备方法EXAMPLE 3 This example illustrates the preparation of compound 30 in Table 1.
Figure PCTCN2018123428-appb-000050
Figure PCTCN2018123428-appb-000050
N-乙基-6-甲砜基-3-硝基吡啶-2-胺(表1中化合物30)N-乙基-6-甲硫基-3-硝基吡啶-2-胺(4mmol)，间氯过氧苯甲酸(10mmol)和二氯甲烷(10mL)，于25℃至体系回流温度反应至完全，加冰盐水，分出有机相，水相经二氯甲烷萃取，合并有机相并经水洗和无水硫酸钠干燥，脱除溶剂，粗产品经柱层析(石油醚+乙酸乙酯为洗脱剂)提纯，得标题物0.62g。N-ethyl-6-methylsulfonyl-3-nitropyridin-2-amine (Compound 30 in Table 1) N-ethyl-6-methylthio-3-nitropyridin-2-amine (4 mmol) , m-chloroperoxybenzoic acid (10 mmol) and dichloromethane (10 mL) were reacted to completion at 25 ° C to reflux temperature, iced brine was added, the organic phase was separated, and the aqueous phase was extracted with dichloromethane. After washing with water and dried over anhydrous sodium sulfate, the solvent was evaporated.
实施例4 本实施例说明表1中化合物98的制备方法EXAMPLE 4 This example illustrates the preparation of compound 98 in Table 1.
Figure PCTCN2018123428-appb-000051
Figure PCTCN2018123428-appb-000051
N-(1-苯基乙基)-6-氯-3-硝基吡啶-2-胺2,6-二氯-3-硝基吡啶(10mmol)，碳酸钾(10mmol)、乙醇(20mL)与1-苯基乙胺(10mmol)的乙醇溶液于0℃至50℃反应至完全。反应混合物倒入冰盐水中，乙酸乙酯萃取，合并有机相并经水洗和无水硫酸钠干燥，脱除溶剂，得粗产品1.95g，不经纯化直接用于下一步合成。N-(1-phenylethyl)-6-chloro-3-nitropyridin-2-amine 2,6-dichloro-3-nitropyridine (10 mmol), potassium carbonate (10 mmol), ethanol (20 mL) The reaction with 1-phenylethylamine (10 mmol) in ethanol was carried out at 0 ° C to 50 ° C until complete. The reaction mixture was poured into EtOAc (EtOAc)EtOAc.
N-(1-苯基乙基)-6-甲硫基-3-硝基吡啶-2-胺(表1中化合物98)N-(1-苯基乙基)-6-氯-3-硝基吡啶-2-胺(8mmol)，25％甲硫醇钠溶液(5mL)和四氢呋喃(10mL)，于0℃至50℃反应至完全后，加入冰盐水，乙酸乙酯萃取，合并有机相并经水洗和无水硫酸钠干燥，脱除溶剂，粗产品经柱层析(石油醚+乙酸乙酯为洗脱剂)提纯，得标题物1.15g。N-(1-phenylethyl)-6-methylthio-3-nitropyridin-2-amine (Compound 98 in Table 1) N-(1-phenylethyl)-6-chloro-3- Nitropyridin-2-amine (8mmol), 25% sodium thiomethoxide solution (5mL) and tetrahydrofuran (10mL), after reacting at 0 ° C to 50 ° C to complete, add ice brine, ethyl acetate extraction, combined organic phase The mixture was washed with water and dried over anhydrous sodium sulfate and evaporated.
实施例5 本实施例说明表1中化合物100的制备方法EXAMPLE 5 This example illustrates the preparation of compound 100 in Table 1.
Figure PCTCN2018123428-appb-000052
Figure PCTCN2018123428-appb-000052
N-(1-苯基乙基)-6-甲砜基-3-硝基吡啶-2-胺(表1中化合物100)N-(1-苯基乙基)-6-甲硫基-3-硝基吡啶-2-胺(4mmol)，间氯过氧化苯甲酸(10mmol)和二氯甲烷(10mL)，于25℃至体系回流温度反应至完全后，加冰盐水，分液，二氯甲烷萃取水层，合并有机相并经水洗和无水硫酸钠干燥，脱除溶剂，粗产品经柱层析(石油醚+乙酸乙酯为洗脱剂)提纯，得标题物0.62g。N-(1-phenylethyl)-6-methylsulfonyl-3-nitropyridin-2-amine (Compound 100 in Table 1) N-(1-phenylethyl)-6-methylthio- 3-nitropyridin-2-amine (4mmol), m-chloroperoxybenzoic acid (10mmol) and dichloromethane (10mL), reacted at 25 ° C to the reflux temperature of the system to complete, add ice brine, liquid separation, two The aqueous layer was extracted with chloromethane. EtOAc was evaporated.
实施例6 本实施例说明表1中化合物101的制备方法EXAMPLE 6 This example illustrates the preparation of compound 101 in Table 1.
Figure PCTCN2018123428-appb-000053
Figure PCTCN2018123428-appb-000053
(R)-N-(1-苯基乙基)-6-氯-3-硝基吡啶-2-胺2,6-二氯-3-硝基吡啶(10mmol)，碳酸钾(10mmol)、乙醇(20mL)与(R)-1-苯基乙胺(10mmol)的乙醇溶液于0℃至50℃反应至完全。反应混合物倒入冰盐水中，乙酸乙酯萃取，合并有机相并经水洗和无水硫酸钠干燥，脱除溶剂，得粗产品1.65g，不经纯化直接用于下一步合成。(R)-N-(1-phenylethyl)-6-chloro-3-nitropyridin-2-amine 2,6-dichloro-3-nitropyridine (10 mmol), potassium carbonate (10 mmol), A solution of ethanol (20 mL) and (R)-1-phenylethylamine (10 mmol) in ethanol was reacted to completion at 0 °C to 50 °C. The reaction mixture was poured into EtOAc (EtOAc)EtOAc.
(R)-N-(1-苯基乙基)-6-甲硫基-3-硝基吡啶-2-胺(表1中化合物101)(R)-2-N-(1-苯基乙基)-6-氯-3-硝基吡啶-2-胺(8mmol)，25％甲硫醇钠溶液(5mL)和四氢呋喃(10mL)于0℃至50℃反应至完全后，加入冰盐水，乙酸乙酯萃取，合并有机相并经水洗和无水硫酸钠干燥，脱除溶剂，粗产品经柱层析(石油醚+乙酸乙酯为洗脱剂)提纯，得标题 物0.86g。(R)-N-(1-phenylethyl)-6-methylthio-3-nitropyridin-2-amine (Compound 101 in Table 1) (R)-2-N-(1-phenyl Ethyl)-6-chloro-3-nitropyridin-2-amine (8 mmol), 25% sodium thiomethoxide solution (5 mL) and tetrahydrofuran (10 mL) were reacted at 0 ° C to 50 ° C until complete. The organic layer was combined with EtOAc (EtOAc)EtOAc.
实施例7 本实施例说明表1中化合物103的制备方法EXAMPLE 7 This example illustrates the preparation of compound 103 in Table 1.
Figure PCTCN2018123428-appb-000054
Figure PCTCN2018123428-appb-000054
(R)-N-(1-苯基乙基)-6-甲砜基-3-硝基吡啶-2-胺(表1中化合物103)(R)-N-(1-苯基乙基)-6-甲硫基-3-硝基吡啶-2-胺(4mmol)，间氯过氧化苯甲酸(10mmol)和二氯甲烷(10mL)，于25℃至体系回流温度反应至完全后，加冰盐水，分液，二氯甲烷萃取水层，合并有机相并经水洗和无水硫酸钠干燥，脱除溶剂，粗产品经柱层析(石油醚+乙酸乙酯为洗脱剂)提纯，得标题物0.50g。(R)-N-(1-phenylethyl)-6-methylsulfonyl-3-nitropyridin-2-amine (Compound 103 in Table 1) (R)-N-(1-phenylethyl - 6-Methylthio-3-nitropyridin-2-amine (4 mmol), m-chloroperoxybenzoic acid (10 mmol) and dichloromethane (10 mL), after reacting to complete at 25 ° C to reflux temperature. The mixture was combined with EtOAc (EtOAc/EtOAcEtOAcEtOAc. The title was 0.50g.
实施例8 本实施例说明表1中化合物242的制备方法EXAMPLE 8 This example illustrates the preparation of compound 242 in Table 1.
Figure PCTCN2018123428-appb-000055
Figure PCTCN2018123428-appb-000055
N-苯基乙基-6-氯-3-硝基吡啶-2-胺2,6-二氯-3-硝基吡啶(10mmol)，碳酸钾(10mmol)、乙醇(20mL)与苯乙胺(10mmol)的乙醇溶液于0℃至50℃反应至完全。反应混合物倒入冰盐水中，乙酸乙酯萃取，合并有机相并经水洗和无水硫酸钠干燥，脱除溶剂，得标题化合物粗产品2.35克，不经纯化直接用于下一步合成。N-phenylethyl-6-chloro-3-nitropyridin-2-amine 2,6-dichloro-3-nitropyridine (10 mmol), potassium carbonate (10 mmol), ethanol (20 mL) and phenethylamine The (10 mmol) ethanol solution was reacted to completion at 0 °C to 50 °C. The reaction mixture was poured into EtOAc EtOAc.
N-苯基乙基-6-甲硫基-3-硝基吡啶-2-胺(表1中化合物242)N-苯基乙基-6-氯-3-硝基吡啶-2-胺(8mmol)，25％甲硫醇钠溶液(5mL)和四氢呋喃(20mL)于0℃至50℃反应至完全后，倒入冰水中，乙酸乙酯萃取，合并有机相并经水洗和无水硫酸钠干燥，脱除溶剂，粗产品经柱层析(石油醚+乙酸乙酯为洗脱剂)提纯，得标题物1.15g。N-phenylethyl-6-methylthio-3-nitropyridin-2-amine (Compound 242 in Table 1) N-phenylethyl-6-chloro-3-nitropyridin-2-amine ( 8mmol), 25% sodium thiomethoxide solution (5mL) and tetrahydrofuran (20mL) were reacted to complete at 0 ° C to 50 ° C, poured into ice water, extracted with ethyl acetate, and the organic phase was washed with water and anhydrous sodium sulfate After drying, the solvent was evaporated. EtOAc m.
实施例9 本实施例说明表1中化合物243的制备方法EXAMPLE 9 This example illustrates the preparation of compound 243 in Table 1.
Figure PCTCN2018123428-appb-000056
Figure PCTCN2018123428-appb-000056
N-苯基乙基-6-甲亚砜基-3-硝基吡啶-2-胺(表1中化合物243)N-苯基乙基-6-甲硫基-3-硝基吡啶-2-胺(4mmol)，间氯过氧苯甲酸(4mmol)和二氯甲烷(10mL)，于0℃至35℃反应至完全，加冰盐水，分出有机相，水相经二氯甲烷萃取，合并有机相，并经水洗和无水硫酸钠干燥，脱除溶剂，粗产品经柱层析(石油醚+乙酸乙酯为洗脱剂)提纯，得标题物0.51g。N-phenylethyl-6-methylsulfoxide-3-nitropyridin-2-amine (Compound 243 in Table 1) N-phenylethyl-6-methylthio-3-nitropyridine-2 -amine (4 mmol), m-chloroperoxybenzoic acid (4 mmol) and dichloromethane (10 mL), EtOAc EtOAc (EtOAc) The combined organic phases were dried with EtOAc EtOAc m.
实施例10 本实施例说明表1中化合物244的制备方法EXAMPLE 10 This example illustrates the preparation of compound 244 in Table 1.
Figure PCTCN2018123428-appb-000057
Figure PCTCN2018123428-appb-000057
N-苯基乙基-6-甲砜基-3-硝基吡啶-2-胺(表1中化合物244)N-苯基乙基-6-甲硫基-3-硝基吡啶-2-胺(4mmol)，间氯过氧化苯甲酸(10mmol)和二氯甲烷(10mL)，于25℃至体系回流温度反应至完全后，加冰盐水，分液，二氯甲烷萃取水层，合并有机相并经水洗和无水硫酸钠干燥，脱除溶剂，粗产品经柱层析(石油醚+乙酸乙酯为洗脱剂)提纯，得标题物0.58g。N-phenylethyl-6-methylsulfonyl-3-nitropyridin-2-amine (Compound 244 in Table 1) N-phenylethyl-6-methylthio-3-nitropyridine-2- Amine (4mmol), m-chloroperoxybenzoic acid (10mmol) and dichloromethane (10mL), after reaction at 25 ° C to the reflux temperature of the system to complete, add ice brine, separate the liquid, extract the aqueous layer with dichloromethane, and combine organic The mixture was washed with water and dried over anhydrous sodium sulfate.
生物活性测定实施例Biological activity assay example
对所合成化合物进行了杀菌、杀虫/螨试验，部分实验结果如下。The synthesized compounds were sterilized and tested for insecticidal/sputum. The results of some experiments are as follows.
实施例11 对小麦赤霉病菌(Gibberella zeae)的杀菌活性Example 11 Bactericidal activity against Gibberella zeae
方法：待测化合物溶于适宜溶剂如N,N-二甲基甲酰胺(DMF)中，再用含0.2％Tween80乳化剂的无菌水稀释至所需浓度，设不含待测化合物的空白为对照，每处理4次重复；用移液管取3mL药液加入冷却至45℃的27mL马铃薯琼脂培养基(PDA)中并充分摇匀后倒入培养皿；冷却后用接种针从培养7天的病菌菌落边缘取6mm直径菌丝块，移至培养皿中央，菌丝面朝下；处理完毕后将培养皿置于28℃的恒温生化培养箱中培养，4天后测量菌丝生长直径，采用EXCEL统计软件进行分析并计算菌丝生长抑制率(％)。活性相对于空白对照以百分比计，分为A、B、C、D四级，100≥抑制率(％)≥90为A级，90＞抑制率(％)≥70为B级，70＞抑制率(％)≥50为C级，50＞抑制率(％)≥0为D级。Method: The test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and then diluted to the desired concentration with sterile water containing 0.2% Tween80 emulsifier, and a blank containing no test compound is provided. For the control, repeat 4 times per treatment; pipette 3 mL of the drug solution into 27 mL potato agar medium (PDA) cooled to 45 ° C and shake well, then pour into the culture dish; after cooling, use the inoculating needle from the culture 7 Take 6mm diameter hyphae on the edge of the pathogen of the day, move to the center of the culture dish, and the hyphae face down. After the treatment, the culture dish is placed in a constant temperature biochemical incubator at 28 °C, and the mycelial growth diameter is measured after 4 days. The EXCEL statistical software was used for analysis and the mycelial growth inhibition rate (%) was calculated. The activity is divided into four grades A, B, C, and D with respect to the blank control, 100 ≥ inhibition rate (%) ≥ 90 is A grade, 90 > inhibition rate (%) ≥ 70 is B grade, 70 > inhibition Rate (%) ≥ 50 is C level, 50> inhibition rate (%) ≥ 0 is D level.
采用上述对小麦赤霉病菌(Gibberella zeae)杀菌活性的测定方法，分别测定了所合成化合物对辣椒疫霉病菌(phytophythora capsici)、黄瓜灰霉病菌(Botrytis cinerea)、油菜菌核病菌(Sclerotonia sclerotiorum)的杀菌活性。Using the above-mentioned method for determining the bactericidal activity of Gibberella zeae, the synthesized compounds were determined for phytophythora capsici, Botrytis cinerea, and Sclerotonia sclerotiorum. Bactericidal activity.
结果表明本发明化合物对上述病菌具有活性，下面是部分结果：The results indicate that the compounds of the present invention are active against the above-mentioned pathogens, and the following are partial results:
25mg/L测试浓度下，化合物03、29、45、54、96、97、243、246、339、340、343、1096等对小麦赤霉病菌具有A级活性，化合物30、32、38、39、91、333等对小麦赤霉病菌具有B级活性，化合物01、04、06、28、33、35、36、43、100、103、165、166、247、270、279、280、328、334、336、342、345等对小麦赤霉病菌具有C级活性；10mg/L测试浓度下，化合物29等对小麦赤霉病菌具有B级活性；化合物30、35、38、246等对小麦赤霉病菌具有C级活性；2.5mg/L测试浓度下，化合物29等对小麦赤霉病菌具有C级活性。At the test concentration of 25mg/L, compounds 03, 29, 45, 54, 96, 97, 243, 246, 339, 340, 343, 1096 have Class A activity against Fusarium graminearum, compounds 30, 32, 38, 39 , 91, 333, etc. have class B activity against Fusarium graminearum, compounds 01, 04, 06, 28, 33, 35, 36, 43, 100, 103, 165, 166, 247, 270, 279, 280, 328, 334, 336, 342, 345 and so on have C-class activity against Fusarium graminearum; at the test concentration of 10 mg/L, Compound 29 has Class B activity against Fusarium graminearum; Compounds 30, 35, 38, 246, etc. Mold fungi have class C activity; compound 2.5 and the like have class C activity against Fusarium graminearum at a concentration of 2.5 mg/L.
25mg/L测试浓度下，化合物03、29、30、54、171、172、243等对辣椒疫霉病菌具有A级活性，化合物30、32、33、35、36、38、39、48、96、97、100、333、334、340等对辣椒疫霉病菌具有B级活性，化合物45、85、89、103、165、166、244、246、252、270、279、328、336、337、339、343、342、345、1094等对辣椒疫霉病菌具有C级活性；10mg/L测试浓度下，化合物29、30等对辣椒疫霉病菌具有B级活性；化合物32、33、35、36、38、39、54、96、97、243等对辣椒疫霉病菌具有C级活性；5mg/L测试浓度下，化合物96等对辣椒疫霉病菌具有C级活性。At the test concentration of 25mg/L, compounds 03, 29, 30, 54, 171, 172, 243 have Class A activity against Phytophthora capsici, compounds 30, 32, 33, 35, 36, 38, 39, 48, 96 , 97, 100, 333, 334, 340, etc. have class B activity against Phytophthora capsici, compounds 45, 85, 89, 103, 165, 166, 244, 246, 252, 270, 279, 328, 336, 337, 339, 343, 342, 345, 1094, etc. have C-class activity against Phytophthora capsici; at the test concentration of 10 mg/L, compounds 29 and 30 have class B activity against Phytophthora capsici; compounds 32, 33, 35, 36 38, 39, 54, 96, 97, 243, etc. have C-class activity against Phytophthora capsici; at the test concentration of 5 mg/L, compound 96 has C-level activity against Phytophthora capsici.
25mg/L测试浓度下，化合物29、30、36、246、342、345等对黄瓜灰霉病菌具有A级活性，化合物01、28、29、32、35、38、45、48、54、89、96、100、171、243、252、270、279、328、343等对黄瓜灰霉病菌具有B级活性，化合物03、04、33、39、43、97、103、280、333、334、335、337、339、340、341、495、496、510、1096等对黄瓜灰霉病菌具有C级活性；10mg/L测试浓度下，化合物01、28、29、30、35、36、89等对黄瓜灰霉病菌具有B级活性；化合物32、38、45、96、243、246等对黄瓜灰霉病菌具有C级活性；5mg/L测试浓度下，化合物01、28、29、32、35、36、38等对黄瓜灰霉病菌具有C级活性。At the test concentration of 25mg/L, compounds 29, 30, 36, 246, 342, 345 have Class A activity against Botrytis cinerea, compounds 01, 28, 29, 32, 35, 38, 45, 48, 54, 89 , 96, 100, 171, 243, 252, 270, 279, 328, 343, etc. have class B activity against Botrytis cinerea, compounds 03, 04, 33, 39, 43, 97, 103, 280, 333, 334, 335, 337, 339, 340, 341, 495, 496, 510, 1096 have C-level activity against Botrytis cinerea; at the test concentration of 10 mg/L, compounds 01, 28, 29, 30, 35, 36, 89, etc. Grade B activity against Botrytis cinerea; Compounds 32, 38, 45, 96, 243, 246 have Class C activity against Botrytis cinerea; Compounds 01, 28, 29, 32, 35 at 5 mg/L test concentration , 36, 38, etc. have C-class activity against Botrytis cinerea.
25mg/L测试浓度下，化合物03、29、30、32、33、36、38、45、54、91、96、97、246、247、328、341、343、345、1096等对油菜菌核病菌具有A级活性，化合物29、35、39、48、89、100、103、243、270、333、342等对油菜菌核病菌具有B级活性，化合物01、04、101、166、171、242、244、252、271、279、280、334、337、339、340、344、496等对油菜菌核病菌具有C级活性；10mg/L测试浓度下，化合物30、33、328等对油菜菌核病菌具有A级活性，化合物29、30、36、45、333等对油菜菌核病菌具有B级活性，化合物35、38、39、54、89、100等对油菜菌核病菌具有C级活性；5mg/L测试浓度下，化合物29、30、33、328等对油菜菌核病菌具有B级活性，化合物30、36、38、39、45、89、333等对油菜菌核病菌具有C级活性；2.5mg/L测试浓度下，化合物29、30、33等对油菜菌核病菌具有C级活性。Compounds 03, 29, 30, 32, 33, 36, 38, 45, 54, 91, 96, 97, 246, 247, 328, 341, 343, 345, 1096, etc. against rape sclerotia at 25 mg/L test concentration The pathogen has class A activity, and compounds 29, 35, 39, 48, 89, 100, 103, 243, 270, 333, 342 have class B activity against Sclerotinia sclerotiorum, compounds 01, 04, 101, 166, 171, 242, 244, 252, 271, 279, 280, 334, 337, 339, 340, 344, 496 have C-class activity against Sclerotinia sclerotiorum; at 10 mg/L test concentration, compounds 30, 33, 328, etc. Sclerotinia sclerotiorum has class A activity, compounds 29, 30, 36, 45, 333 have class B activity against Sclerotinia sclerotiorum, and compounds 35, 38, 39, 54, 89, 100 have C grade for Sclerotinia sclerotiorum Activity; at the test concentration of 5mg/L, compounds 29, 30, 33, 328 have B-level activity against Sclerotinia sclerotiorum, and compounds 30, 36, 38, 39, 45, 89, 333 have C against Sclerotinia sclerotiorum Grade activity; Compounds 29, 30, 33, etc. have class C activity against Sclerotinia sclerotiorum at a concentration of 2.5 mg/L.
实施例12 对黄瓜灰霉病(Botrytis cinerea)的防治效果(盆栽法)Example 12 Control effect on cucumber gray mold (Botrytis cinerea) (potted method)
方法：待测化合物溶于适宜溶剂如N,N-二甲基甲酰胺(DMF)中，再用含0.2％Tween80乳化剂的无菌水稀释至所需浓度，设不含待测化合物的空白为对照，每处理4次重复；将黄瓜灰霉病原菌转至PDA平板活化培养后转至PD培养基中，恒温水浴培养4天；将培养好的菌丝球用匀浆机粉碎并用清水调配至一定浓度的菌悬液；待黄瓜长至展平两片真叶时，喷施上述待测化合物的药液，1天后喷施菌悬液至幼苗表面，保湿培养并观察幼苗发 病情况，当对照处理发病明显，开始记载各处理的发病情况，计算药剂防效。结果表明本发明的化合物对黄瓜灰霉病具有防治效果。下面是部分结果：500mg/L剂量下，化合物343等对黄瓜灰霉病具有95％以上的防治活性，化合物244、243、270、337等对黄瓜灰霉病具有80％以上的防治活性，化合物48、328等对黄瓜灰霉病具有70％以上的防治活性。Method: The test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and then diluted to the desired concentration with sterile water containing 0.2% Tween80 emulsifier, and a blank containing no test compound is provided. For the control, the treatment was repeated 4 times; the Cucumber ash pathogen was transferred to the PDA plate and cultured, transferred to the PD medium, and cultured in a constant temperature water bath for 4 days; the cultured hyphae ball was pulverized with a homogenizer and formulated with water. a certain concentration of bacterial suspension; when the cucumber grows to flatten two true leaves, spray the above-mentioned test compound liquid, spray the bacterial suspension to the surface of the seedling after 1 day, moisturize and observe the seedling incidence, when the control The treatment was obvious, and the onset of each treatment was recorded, and the drug control effect was calculated. The results show that the compound of the present invention has a control effect against cucumber gray mold. The following are partial results: at the dose of 500mg/L, compound 343 has more than 95% control activity against cucumber gray mold, and compounds 244, 243, 270, 337 have more than 80% control activity against cucumber gray mold, compound 48, 328, etc. have more than 70% control activity against cucumber gray mold.
实施例13 对玉米锈病(Puccinia Polysora)的防治效果(盆栽法)Example 13 Control effect on corn rust (Puccinia Polysora) (pot method)
方法：待测化合物溶于适宜溶剂如N,N-二甲基甲酰胺(DMF)中，再用含0.2％Tween80乳化剂的无菌水稀释至所需浓度，设不含待测化合物的空白为对照，每处理4次重复；剪下发病玉米叶片，用0.05％Tween80或其它合适表面活性剂水溶液洗下孢子，并用2～4层纱布过滤，制成浓度为1×10 5个孢子/mL的悬浮液；待玉米长至2叶1心期，喷施上述待测化合物的药液，1天后孢子悬浮液喷雾接种，接种后移至保湿柜(相对湿度95％以上，温度20℃～22℃)，弱光条件下(光照强度5 000Lux～10000Lux)培养15～24hr；待空白对照病叶率达50％以上时，调查各处理的发病情况，计算药剂防效。结果表明本发明的化合物对玉米锈病具有防治效果。下面列出部分结果： Method: The test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and then diluted to the desired concentration with sterile water containing 0.2% Tween80 emulsifier, and a blank containing no test compound is provided. For the control, repeat 4 times per treatment; cut the affected corn leaves, wash the spores with 0.05% Tween80 or other suitable surfactant aqueous solution, and filter with 2 to 4 layers of gauze to make a concentration of 1 × 10 5 spores / mL Suspension; wait until the corn grows to 2 leaves 1 heart period, spray the above-mentioned test compound liquid, spray the inoculation of spore suspension 1 day later, and inoculate it to the moisturizing cabinet after inoculation (relative humidity 95% or more, temperature 20 ° C ~ 22 °C), under low light conditions (light intensity 5 000 Lux ~ 10000 Lux) cultured for 15 ~ 24hr; when the leaf rate of the blank control disease reached 50% or more, investigate the incidence of each treatment, calculate the drug control effect. The results indicate that the compound of the present invention has a control effect on corn rust. Some of the results are listed below:
500mg/L剂量下，化合物29、48、100、243、244、336、337、339、340等对玉米锈病具有90％以上的防治活性；化合物30、46、98、253、280、334、346等对玉米锈病具有80％以上的防治活性；化合物274、510等对玉米锈病具有70％以上的防治活性。At doses of 500 mg/L, compounds 29, 48, 100, 243, 244, 336, 337, 339, 340, etc. have more than 90% control activity against corn rust; compounds 30, 46, 98, 253, 280, 334, 346 It has more than 80% control activity against corn rust; compounds 274, 510 have more than 70% control activity against corn rust.
100mg/L剂量下，化合物29、100、243、244等对玉米锈病具有90％以上的防治活性。At doses of 100 mg/L, compounds 29, 100, 243, 244, etc. have more than 90% control activity against corn rust.
50mg/L剂量下，化合物243、244等对玉米锈病具有80％以上的防治活性。At the dose of 50 mg/L, the compounds 243, 244 and the like have more than 80% control activity against corn rust.
25mg/L剂量下，化合物243、244等对玉米锈病具有70％以上的防治活性。At the dose of 25 mg/L, the compounds 243, 244 and the like have a control activity against corn rust of 70% or more.
式(B)、式(C)和式(D)所示苯基砜或其衍生物在100mg/L剂量下，对玉米锈病的防效均不超过50％。The phenyl sulfone or its derivative represented by the formula (B), the formula (C) and the formula (D) does not have a control effect on corn rust at a dose of 100 mg/L of not more than 50%.
实施例14 对水稻纹枯病(Rhizoctonia solani)的防治效果Example 14 Control effect on rice sheath blight (Rhizoctonia solani)
方法：参照上述对黄瓜灰霉病的防治效果评价方法，测试了本发明化合物对水稻纹枯病(Rhizoctonia solani)的防治效果。结果表明本发明的化合物对水稻纹枯病具有防治效果，下面列出部分结果：Method: The control effect of the compound of the present invention on Rhizoctonia solani was tested with reference to the above-mentioned evaluation method for the control effect of Cucumber gray mold. The results show that the compounds of the present invention have a control effect on rice sheath blight, and some results are listed below:
500mg/L剂量下，化合物29、30、85、97、100、244、252、337等对水稻纹枯病具有90％以上的防治活性；化合物83、97、171、243、246、270、328、339、343、344等对水稻纹枯病具有80％以上的防治活性；化合物247、333、334、340、342等对水稻纹枯病具有70％以上的防治活性。At doses of 500 mg/L, compounds 29, 30, 85, 97, 100, 244, 252, 337 and the like have more than 90% control activity against rice sheath blight; compounds 83, 97, 171, 243, 246, 270, 328 339, 343, 344, etc. have more than 80% control activity against rice sheath blight; compounds 247, 333, 334, 340, 342 have more than 70% control activity against rice sheath blight.
100mg/L剂量下，化合物97、252、244等对水稻纹枯病具有90％以上的防治活性；83、85、243等对水稻纹枯病具有70％以上的防治活性。At the dose of 100mg/L, compounds 97, 252, and 244 have more than 90% control activity against rice sheath blight; 83, 85, and 243 have more than 70% control activity against rice sheath blight.
50mg/L剂量下，化合物244等对水稻纹枯病具有90％以上的防治活性；化合物97等对水稻纹枯病具有80％以上的防治活性；化合物83、85、243、252等对水稻纹枯病具有70％以上的防治活性。At the dose of 50mg/L, compound 244 has more than 90% control activity against rice sheath blight; compound 97 has more than 80% control activity against rice sheath blight; compound 83, 85, 243, 252, etc. Blight has more than 70% control activity.
式(B)、式(C)和式(D)所示苯基砜或其衍生物在100mg/L剂量下，对水稻纹枯病的防效均不超过50％；式(B)、式(C)和式(D)所示苯基砜或其衍生物在50mg/L剂量下，对水稻纹枯病的防效均不超过30％。The phenyl sulfone or its derivative represented by formula (B), formula (C) and formula (D) has a control effect against rice sheath blight at a dose of 100 mg/L of not more than 50%; formula (B), formula The phenyl sulfone or its derivative represented by (C) and formula (D) does not have a control effect against rice sheath blight at a dose of 50 mg/L of not more than 30%.
实施例15 对小麦白粉病菌(Erisiphe griminis)的杀菌活性(盆栽法)Example 15 Bactericidal activity against wheat white powder pathogen (Erisiphe griminis) (pot method)
方法：待测化合物溶于适宜溶剂如N,N-二甲基甲酰胺(DMF)中，再用含0.2％Tween80乳化剂的无菌水稀释至所需浓度，设不含待测化合物的空白为对照；取直茎15cm左右的盆钵，每钵播种小麦饱满健壮的种子20粒，待长出二叶一心后供试验用；取准备好的小麦幼苗植株经一定浓度的药剂喷雾处理，一天后进行病菌接种。每处理3次重复，另设不含待测化合物的空白为对照，保湿适温培养至空白对照发病后，检查病斑面积，计算药剂防效。活性相对空白对照以百分比计。Method: The test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and then diluted to the desired concentration with sterile water containing 0.2% Tween80 emulsifier, and a blank containing no test compound is provided. For the control; take the pots with a stem of about 15cm, and soak the seeds of 20 full and healthy seeds of wheat, and use them for the test after growing the leaves; take the prepared wheat seedlings with a certain concentration of spray treatment, one Inoculation of the bacteria after the day. Each treatment was repeated 3 times, and a blank containing no test compound was set as a control. After moisturizing and warming culture until the onset of the blank control, the area of the lesion was examined and the drug control effect was calculated. Activity is relative to the blank control as a percentage.
结果表明本发明的化合物对小麦白粉病具有防治效果。下面列出部分结果：The results indicate that the compound of the present invention has a control effect against wheat powdery mildew. Some of the results are listed below:
500mg/L剂量下，化合物341、343等对小麦白粉病具有90％以上的防效；化合物168、246、344、510等对小麦白粉病具有80％以上的防效；化合物247、252等对小麦白粉病具有70％以上的防效。At the dose of 500mg/L, compounds 341 and 343 have more than 90% control effect on wheat powdery mildew; compounds 168, 246, 344, 510 have more than 80% control effect on wheat powdery mildew; compounds 247, 252, etc. Wheat powdery mildew has more than 70% control effect.
式(B)、式(C)和式(D)所示的苯基砜或其衍生物在500mg/L浓度下，对小麦白粉病的防效均为0％。The phenyl sulfone or the derivative thereof represented by the formula (B), the formula (C) and the formula (D) has a control effect against wheat powdery mildew of 0% at a concentration of 500 mg/L.
实施例16 对蚜虫(Aphi s spp.)的杀虫活性评价Example 16 Evaluation of insecticidal activity against aphids (Aphi s spp.)
为评价本发明化合物对同翅目害虫的活性，选择蚜虫为对象，采用浸渍法测定了本发明化合物对蚜虫的活性。In order to evaluate the activity of the compound of the present invention against Homoptera pests, the aphid was selected as a subject, and the activity of the compound of the present invention against aphids was measured by a dipping method.
浸渍法：待测化合物溶于适宜溶剂如N,N-二甲基甲酰胺(DMF)中，再用含0.2％Tween80乳化剂的清水稀释至所需浓度，设不含待测化合物的空白为对照，每处理3次重复。将蚕豆蚜(Aphis fabae)接于刚出土的豆苗上，每株接20头以上，然后将豆苗连同试虫一起浸于本发明提供的式(I)药液中，5秒钟后取出，吸去多余药液，***吸水的海棉中，用玻管罩住，24小时后检查存活和死亡虫数，结果取平均值。活性(死亡率)相对空白对照以百分比计，分为A、B、C、D四级，100≥死亡率(％)≥90为A级，90＞死亡率(％)≥70为B级，70＞死亡率(％)≥50为C级，50＞死亡率(％)≥0为D级。结果表明本发明的化合物对蚕豆蚜具有活性，下面列出部分结果：Impregnation method: The test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and diluted with water containing 0.2% Tween80 emulsifier to the desired concentration, and the blank containing no test compound is Control, repeated 3 times per treatment. The Aphis fabae is attached to the newly-extracted bean seedlings, and each plant is connected to more than 20 heads. Then, the bean seedlings are immersed together with the test insects in the liquid of the formula (I) provided by the present invention, and taken out after 5 seconds. The excess liquid was aspirated, inserted into the absorbent sponge, covered with a glass tube, and the number of surviving and dead insects was checked after 24 hours, and the results were averaged. The activity (mortality) was divided into four levels A, B, C, and D, and 100% ≥ mortality (%) ≥ 90 for grade A, 90 > mortality (%) ≥ 70 for grade B, relative to the blank control. 70> Mortality (%) ≥ 50 is C grade, 50 > mortality (%) ≥ 0 is D grade. The results indicate that the compounds of the present invention are active against broad bean meal, and some of the results are listed below:
500mg/L浓度下，化合物165、172等对蚜虫具A级活性；化合物46、247、279、326、 341、343、495等对蚜虫具B级活性；化合物52、54、166、246、332、344、345、494、524等对蚜虫具C级活性。At the concentration of 500mg/L, compounds 165 and 172 have Class A activity against aphids; Compounds 46, 247, 279, 326, 341, 343, 495 have Class B activity against aphids; Compounds 52, 54, 166, 246, 332 344, 345, 494, 524, etc. have class C activity on aphids.
200mg/L浓度下，化合物172等对蚜虫具有B级活性；化合物165等对蚜虫具有C级活性。At a concentration of 200 mg/L, compound 172 or the like has a class B activity against aphids; compound 165 or the like has a class C activity on aphids.
式(B)、式(C)和式(D)所示的苯基砜或其衍生物在500mg/L浓度下，对蚜虫的死亡率均低于50％。The phenyl sulfone or the derivative thereof represented by the formula (B), the formula (C) and the formula (D) has a mortality rate against aphids of less than 50% at a concentration of 500 mg/L.
实施例17 对棉红蜘蛛(Tetranychus urticae)的杀螨活性评价Example 17 Evaluation of acaricidal activity against cotton red spider (Tetranychus urticae)
方法：待测化合物溶于适宜溶剂如N,N-二甲基甲酰胺(DMF)中，再用含0.2％Tween80乳化剂的清水稀释至所需浓度，设不含待测化合物的空白为对照，每处理3次重复。选择长势良好的豆苗接种红蜘蛛，待红蜘蛛定殖后，将带螨豆苗剪下于配制好的本发明提供的式(I)化合物的药液中浸渍10秒，取出用滤纸吸去多余的药液，插于盛水烧杯中，于观察室内培养，48小时后检查存活和死亡螨数，每株豆苗上有100-200个螨。实验重复3次。结果取平均值。活性相对于空白对照以百分比计，分为A、B、C、D四级，分级标准同蚜虫实施例。结果表明本发明的化合物对棉红蜘蛛具有活性，下面列出部分结果：Method: The test compound is dissolved in a suitable solvent such as N,N-dimethylformamide (DMF), and then diluted with the water containing 0.2% Tween80 emulsifier to the desired concentration, and the blank containing no test compound is used as a control. , repeated 3 times for each treatment. Select a good bean seedling to inoculate red spider. After the spider is colonized, the bean seedlings are cut into the prepared liquid of the compound of the formula (I) provided by the present invention for 10 seconds, and taken out with a filter paper. The excess liquid was inserted into a water-filled beaker and cultured in the observation room. After 48 hours, the number of survival and death defects was checked, and there were 100-200 cockroaches per bean seedling. The experiment was repeated three times. The results were averaged. The activity was divided into four grades A, B, C, and D with respect to the blank control, and the classification standard was the same as the aphid example. The results indicate that the compounds of the invention are active against cotton spider mites, and some of the results are listed below:
500mg/L浓度下，化合物36、39等对棉红蜘蛛具A级活性；化合物33、345、495、1114等对棉红蜘蛛具B级活性；化合物168、1096等对棉红蜘蛛具C级活性。At the concentration of 500mg/L, compounds 36, 39 have A-grade activity against cotton red spider; compounds 33, 345, 495, 1114 have B-grade activity against cotton red spider; compounds 168, 1096 and other cotton-red spiders have grade C active.
200mg/L浓度下，化合物345等对棉红蜘蛛具C级活性。At a concentration of 200 mg/L, compound 345 and the like had a class C activity against cotton red spider.
式(B)、式(C)和式(D)所示的苯基砜或其衍生物在500mg/L浓度下，棉红蜘蛛的死亡率均低于15％。The phenyl sulfone or the derivative thereof represented by the formula (B), the formula (C) and the formula (D) has a mortality rate of less than 15% at a concentration of 500 mg/L.
以上所述仅是本发明的优选实施方式，本发明的保护范围并不仅局限于上述实施例。凡属于本发明思路下的技术方案均属于本发明的保护范围。应该指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下的改进和润饰，这些改进和润饰也应视为本发明的保护范围。The above description is only a preferred embodiment of the present invention, and the scope of protection of the present invention is not limited to the above embodiments. All the technical solutions falling under the idea of the present invention belong to the protection scope of the present invention. It should be noted that those skilled in the art will be able to devise modifications and refinements without departing from the principles of the invention.

Claims (10)

  1. 吡啶砜及其衍生物，其特征在于用通式(I)表示吡啶砜及其衍生物：Pyridinone and its derivatives, characterized in that the pyridylsulfone and its derivatives are represented by the general formula (I):
    Figure PCTCN2018123428-appb-100001
    Figure PCTCN2018123428-appb-100001
    其中：among them:
    I.R代表硝基；I.R represents a nitro group;
    II.R 1代表氢、C 1-C 12烷基或C 3-C 6环烷基； II. R 1 represents hydrogen, C 1 -C 12 alkyl or C 3 -C 6 cycloalkyl;
    III.R 2代表氢、卤素、C 1-C 12烷基或C 3-C 6环烷基； III. R 2 represents hydrogen, halogen, C 1 -C 12 alkyl or C 3 -C 6 cycloalkyl;
    IV.R 3代表氢、C 1-C 12烷基、C 2-C 12链烯基、C 2-C 12链炔基或苯基； IV. R 3 represents hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or phenyl;
    V.R 4代表氢、C 1-C 12烷基或C 3-C 6环烷基； VR 4 represents hydrogen, C 1 -C 12 alkyl or C 3 -C 6 cycloalkyl;
    VI.R 5代表氢、C 1-C 12烷基、C 3-C 8环烷基、苯基、苯基甲基、苯基乙基、噻唑基、噻唑基甲基、噻唑基乙基、呋喃基、呋喃基甲基、呋喃基乙基、噻酚基、噻酚基甲基、噻酚基乙基、四氢呋喃基、四氢呋喃基甲基、四氢呋喃基乙基、吡啶基、卤代吡啶基、吡啶基甲基、卤代吡啶基甲基、吡啶基乙基、卤代吡啶基乙基； VI. R 5 represents hydrogen, C 1 -C 12 alkyl, C 3 -C 8 cycloalkyl, phenyl, phenylmethyl, phenylethyl, thiazolyl, thiazolylmethyl, thiazolylethyl, Furanyl, furylmethyl, furylethyl, thiophenol, thiophenoxymethyl, thiophenethyl, tetrahydrofuranyl, tetrahydrofuranylmethyl, tetrahydrofuranylethyl, pyridyl, halopyridyl, Pyridylmethyl, halopyridylmethyl, pyridylethyl, halopyridylethyl;
    VII.n代表0、1或2；m代表1或2；且VII.n represents 0, 1 or 2; m represents 1 or 2;
    1)如在II.、III.、IV.、V.、VI.中所确定的含义，其中0个氢原子、部分氢原子或全部氢原子被选自下列中相同或不同的取代基取代：卤素、C 1-C 12烷基、C 1-C 12烷氧基、苯基、卤代苯基、C 1-C 12烷基苯基、被卤素和C 1-C 6烷基取代苯基； 1) The meaning as defined in II., III., IV., V., VI. wherein 0 hydrogen atoms, partial hydrogen atoms or all hydrogen atoms are substituted by the same or different substituents selected from the group consisting of: Halogen, C 1 -C 12 alkyl, C 1 -C 12 alkoxy, phenyl, halophenyl, C 1 -C 12 alkylphenyl, phenyl substituted by halogen and C 1 -C 6 alkyl ;
    2)硝基为5-硝基时，n不代表0；2) When the nitro group is a 5-nitro group, n does not represent 0;
    3)m＝1时，通式(I)化合物即通式(Ia)化合物；m＝2时，通式(I)化合物即通式(Ib)化合物；3) when m=1, the compound of the formula (I) is a compound of the formula (Ia); when m=2, the compound of the formula (I) is a compound of the formula (Ib);
    Figure PCTCN2018123428-appb-100002
    Figure PCTCN2018123428-appb-100002
    4)通式(I)化合物不代表N-乙基-N-((2-氯噻唑-5-基)甲基)-6-甲硫基-3-硝基吡啶-2-胺和N-环丁基-6-甲硫基-3-硝基吡啶-2-胺；4) The compound of the formula (I) does not represent N-ethyl-N-((2-chlorothiazol-5-yl)methyl)-6-methylthio-3-nitropyridin-2-amine and N- Cyclobutyl-6-methylthio-3-nitropyridin-2-amine;
    上面给出的化合物(I)的定义中，所用术语不论单独使用还是用在复合词中，代表如下取代基：In the definition of the compound (I) given above, the terms used, whether used alone or in a compound, represent the following substituents:
    卤素：指氟、氯、溴、碘；Halogen: means fluorine, chlorine, bromine, iodine;
    烷基：指直链或支链烷基；Alkyl: means a straight or branched alkyl group;
    环烷基：指饱和或不饱和的环烷基；Cycloalkyl: means a saturated or unsaturated cycloalkyl group;
    杂环烷基：指饱和或不饱和的杂环烷基，式中至少有1个N，O和/或S；Heterocycloalkyl: a saturated or unsaturated heterocycloalkyl group having at least one N, O and/or S;
    链烯基；指直链或支链并可在任何位置上存在有双键；Alkenyl; means straight or branched and may have a double bond at any position;
    链炔基；指直链或支链并可在任何位置上存在有三键。Alkynyl; means straight or branched and may have a triple bond at any position.
  2. 根据权利要求1所述的吡啶砜及其衍生物，其特征在于通式(I)所示化合物中：The pyrithione according to claim 1 or a derivative thereof, which is characterized by the compound of the formula (I):
    I.R代表3-硝基；I.R represents 3-nitro;
    II.R 1代表氢或C 1-C 12烷基； II. R 1 represents hydrogen or C 1 -C 12 alkyl;
    III.R 2代表氢、卤素或C 1-C 12烷基； III. R 2 represents hydrogen, halogen or C 1 -C 12 alkyl;
    IV.R 3代表氢、C 1-C 12烷基、C 2-C 12链烯基、C 2-C 12链炔基或苯基； IV. R 3 represents hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or phenyl;
    V.R 4代表氢或C 1-C 12烷基； VR 4 represents hydrogen or C 1 -C 12 alkyl;
    VI.R 5代表氢、C 1-C 12烷基、C 3-C 8环烷基、苯基、苯基甲基、苯基乙基、噻唑基、噻唑基甲基、噻唑基乙基、呋喃基、呋喃基甲基、呋喃基乙基、噻酚基、噻酚基甲基、噻酚基乙基、四氢呋喃基、四氢呋喃基甲基、四氢呋喃基乙基、吡啶基、卤代吡啶基、吡啶基甲基、卤代吡啶基甲基、吡啶基乙基、卤代吡啶基乙基； VI. R 5 represents hydrogen, C 1 -C 12 alkyl, C 3 -C 8 cycloalkyl, phenyl, phenylmethyl, phenylethyl, thiazolyl, thiazolylmethyl, thiazolylethyl, Furanyl, furylmethyl, furylethyl, thiophenol, thiophenoxymethyl, thiophenethyl, tetrahydrofuranyl, tetrahydrofuranylmethyl, tetrahydrofuranylethyl, pyridyl, halopyridyl, Pyridylmethyl, halopyridylmethyl, pyridylethyl, halopyridylethyl;
    VII.n代表0、1或2；m代表1或2；且VII.n represents 0, 1 or 2; m represents 1 or 2;
    1)如在II.、III.、IV.、V.、VI.中所确定的含义，其中0个氢原子、部分氢原子或全部氢原子被选自下列中相同或不同的取代基取代：卤素、C 1-C 12烷基、C 1-C 12烷氧基、苯基、卤代苯基、C 1-C 12烷基苯基、被卤素和C 1-C 6烷基取代苯基； 1) The meaning as defined in II., III., IV., V., VI. wherein 0 hydrogen atoms, partial hydrogen atoms or all hydrogen atoms are substituted by the same or different substituents selected from the group consisting of: Halogen, C 1 -C 12 alkyl, C 1 -C 12 alkoxy, phenyl, halophenyl, C 1 -C 12 alkylphenyl, phenyl substituted by halogen and C 1 -C 6 alkyl ;
    2)硝基为5-硝基时，n不代表0；2) When the nitro group is a 5-nitro group, n does not represent 0;
    3)m＝1时，通式(I)化合物即通式(Ia)化合物；m＝2时，通式(I)化合物即通式(Ib)化合物；3) when m=1, the compound of the formula (I) is a compound of the formula (Ia); when m=2, the compound of the formula (I) is a compound of the formula (Ib);
    Figure PCTCN2018123428-appb-100003
    Figure PCTCN2018123428-appb-100003
    4)通式(I)化合物不代表N-乙基-N-((2-氯噻唑-5-基)甲基)-6-甲硫基-3-硝基吡啶-2-胺和N-环丁基-6-甲硫基-3-硝基吡啶-2-胺。4) The compound of the formula (I) does not represent N-ethyl-N-((2-chlorothiazol-5-yl)methyl)-6-methylthio-3-nitropyridin-2-amine and N- Cyclobutyl-6-methylthio-3-nitropyridin-2-amine.
  3. 根据权利要求1所述吡啶砜及其衍生物，其特征在于通式(I)所示化合物中：The pyrithione according to claim 1 or a derivative thereof, which is characterized by the compound of the formula (I):
    I.R代表3-硝基；I.R represents 3-nitro;
    II.R 1代表氢或C 1-C 12烷基； II. R 1 represents hydrogen or C 1 -C 12 alkyl;
    III.R 2代表氢、卤素或C 1-C 12烷基； III. R 2 represents hydrogen, halogen or C 1 -C 12 alkyl;
    IV.R 3代表氢、C 1-C 12烷基、C 2-C 12链烯基、C 2-C 12链炔基或苯基； IV. R 3 represents hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or phenyl;
    V.R 4代表氢或C 1-C 12烷基； VR 4 represents hydrogen or C 1 -C 12 alkyl;
    VI.R 5代表氢、C 1-C 12烷基、C 3-C 8环烷基、苯基、苯基甲基、苯基乙基、噻唑基、噻唑基甲基、噻唑基乙基、呋喃基、呋喃基甲基、呋喃基乙基、噻酚基、噻酚基甲基、噻酚基乙基、四氢呋喃基、四氢呋喃基甲基、四氢呋喃基乙基、吡啶基、卤代吡啶基、吡啶基甲基、卤代吡啶基甲基、吡啶基乙基、卤代吡啶基乙基； VI. R 5 represents hydrogen, C 1 -C 12 alkyl, C 3 -C 8 cycloalkyl, phenyl, phenylmethyl, phenylethyl, thiazolyl, thiazolylmethyl, thiazolylethyl, Furanyl, furylmethyl, furylethyl, thiophenol, thiophenoxymethyl, thiophenethyl, tetrahydrofuranyl, tetrahydrofuranylmethyl, tetrahydrofuranylethyl, pyridyl, halopyridyl, Pyridylmethyl, halopyridylmethyl, pyridylethyl, halopyridylethyl;
    VII.n代表1或2；m代表1；且VII.n represents 1 or 2; m represents 1;
    1)如在II.、III.、IV.、V.、或VI.中所确定的含义，其中0个氢原子、部分氢原子或全部氢原子被选自下列中相同或不同的取代基取代：卤素、C 1-C 12烷基、C 1-C 12烷氧基、苯基、卤代苯基、C 1-C 12烷基苯基、被卤素和C 1-C 6烷基取代苯基。 1) meaning as defined in II., III., IV., V., or VI. wherein 0 hydrogen atoms, partial hydrogen atoms or all hydrogen atoms are replaced by the same or different substituents selected from the following : halogen, C 1 -C 12 alkyl, C 1 -C 12 alkoxy, phenyl, halophenyl, C 1 -C 12 alkylphenyl, substituted by halogen and C 1 -C 6 alkyl base.
  4. 根据权利要求1所述吡啶砜及其衍生物，其特征在于通式(I)所示化合物中：The pyrithione according to claim 1 or a derivative thereof, which is characterized by the compound of the formula (I):
    I.R代表3-硝基；I.R represents 3-nitro;
    II.R 1代表氢或C 1-C 12烷基； II. R 1 represents hydrogen or C 1 -C 12 alkyl;
    III.R 2代表氢、卤素或C 1-C 12烷基； III. R 2 represents hydrogen, halogen or C 1 -C 12 alkyl;
    IV.R 3代表氢、C 1-C 12烷基、C 2-C 12链烯基、C 2-C 12链炔基或苯基； IV. R 3 represents hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl or phenyl;
    V.R 4代表氢或C 1-C 12烷基； VR 4 represents hydrogen or C 1 -C 12 alkyl;
    VI.R 5代表氢、C 1-C 12烷基、环丙基、苯基、苯基甲基、噻唑基、噻唑基甲基、呋喃基、呋喃基甲基、噻酚基、噻酚基甲基、四氢呋喃基、四氢呋喃基甲基、吡啶基、卤代吡啶基、吡啶基甲基、卤代吡啶基甲基； VI. R 5 represents hydrogen, C 1 -C 12 alkyl, cyclopropyl, phenyl, phenylmethyl, thiazolyl, thiazolylmethyl, furyl, furylmethyl, thiophenol, thiophenol Methyl, tetrahydrofuranyl, tetrahydrofuranylmethyl, pyridyl, halopyridyl, pyridylmethyl, halopyridylmethyl;
    VII.n代表1或2；m代表1；且VII.n represents 1 or 2; m represents 1;
    1)如在II.、III.、IV.、V.、或VI.中所确定的含义，其中苯基上氢原子的0个、部分或全部被选自下列中相同或不同的取代基取代：卤素、C 1-C 12烷基、C 1-C 12烷氧基、苯基、卤代苯基、C 1-C 12烷基苯基、被卤素和C 1-C 6烷基取代苯基。 1) The meaning as defined in II., III., IV., V., or VI. wherein 0, part or all of the hydrogen atom on the phenyl group is substituted with the same or different substituent selected from the following : halogen, C 1 -C 12 alkyl, C 1 -C 12 alkoxy, phenyl, halophenyl, C 1 -C 12 alkylphenyl, substituted by halogen and C 1 -C 6 alkyl base.
  5. 根据权利要求1所述的吡啶砜及其衍生物，其特征在于通式(I)所示化合物是：The pyrithione and derivative thereof according to claim 1, wherein the compound of the formula (I) is:
    N-甲基-6-甲砜基-3-硝基吡啶-2-胺；N-methyl-6-methylsulfonyl-3-nitropyridin-2-amine;
    N-乙基-6-甲硫基-3-硝基吡啶-2-胺；N-ethyl-6-methylthio-3-nitropyridin-2-amine;
    N-乙基-6-甲亚砜基-3-硝基吡啶-2-胺；N-ethyl-6-methylsulfoxide-3-nitropyridin-2-amine;
    N-乙基-6-甲砜基-3-硝基吡啶-2-胺；N-ethyl-6-methylsulfonyl-3-nitropyridin-2-amine;
    N-甲氧乙基-6-甲亚砜基-3-硝基吡啶-2-胺；N-methoxyethyl-6-methylsulfoxide-3-nitropyridin-2-amine;
    N-甲氧乙基-6-甲砜基-3-硝基吡啶-2-胺；N-methoxyethyl-6-methylsulfonyl-3-nitropyridin-2-amine;
    N-乙氧乙基-6-甲亚砜基-3-硝基吡啶-2-胺；N-ethoxyethyl-6-methylsulfoxide-3-nitropyridin-2-amine;
    N-乙氧乙基-6-甲砜基-3-硝基吡啶-2-胺；N-ethoxyethyl-6-methylsulfonyl-3-nitropyridin-2-amine;
    N-(3-甲氧基丙基)-6-甲亚砜基-3-硝基吡啶-2-胺；N-(3-methoxypropyl)-6-methylsulfoxide-3-nitropyridin-2-amine;
    N-(3-甲氧基丙基)-6-甲砜基-3-硝基吡啶-2-胺；N-(3-methoxypropyl)-6-methylsulfonyl-3-nitropyridin-2-amine;
    N-异丙基-6-甲砜基-3-硝基吡啶-2-胺；N-isopropyl-6-methylsulfonyl-3-nitropyridin-2-amine;
    N-丙基-6-甲硫基-3-硝基吡啶-2-胺；N-propyl-6-methylthio-3-nitropyridin-2-amine;
    N-丙基-6-甲砜基-3-硝基吡啶-2-胺；N-propyl-6-methylsulfonyl-3-nitropyridin-2-amine;
    N-正丁基-6-甲砜基-3-硝基吡啶-2-胺；N-n-butyl-6-methylsulfonyl-3-nitropyridin-2-amine;
    N-(四氢呋喃-3-基)甲基-6-甲硫基-3-硝基吡啶-2-胺；N-(tetrahydrofuran-3-yl)methyl-6-methylthio-3-nitropyridin-2-amine;
    N-(四氢呋喃-3-基)甲基-6-甲砜基-3-硝基吡啶-2-胺；N-(tetrahydrofuran-3-yl)methyl-6-methylsulfonyl-3-nitropyridin-2-amine;
    N-(四氢呋喃-2-基)甲基-6-甲砜基-3-硝基吡啶-2-胺；N-(tetrahydrofuran-2-yl)methyl-6-methylsulfonyl-3-nitropyridin-2-amine;
    N-苯基甲基-6-甲亚砜基-3-硝基吡啶-2-胺；N-phenylmethyl-6-methylsulfoxide-3-nitropyridin-2-amine;
    N-苯基甲基-6-甲砜基-3-硝基吡啶-2-胺；N-phenylmethyl-6-methylsulfonyl-3-nitropyridin-2-amine;
    N-(1-苯基乙基)-6-甲砜基-3-硝基吡啶-2-胺；N-(1-phenylethyl)-6-methylsulfonyl-3-nitropyridin-2-amine;
    N-(2-氯噻唑-5-基)甲基-6-甲亚砜基-3-硝基吡啶-2-胺；N-(2-chlorothiazol-5-yl)methyl-6-methylsulfoxide-3-nitropyridin-2-amine;
    N-(2-苯基-4-甲基噻唑-5-基)甲基-6-甲亚砜基-3-硝基吡啶-2-胺；N-(2-phenyl-4-methylthiazol-5-yl)methyl-6-methylsulfoxide-3-nitropyridin-2-amine;
    N-(2-苯基-4-甲基噻唑-5-基)甲基-6-甲砜基-3-硝基吡啶-2-胺；N-(2-phenyl-4-methylthiazol-5-yl)methyl-6-methylsulfonyl-3-nitropyridin-2-amine;
    N-苯基乙基-6-甲亚砜基-3-硝基吡啶-2-胺；N-phenylethyl-6-methylsulfoxide-3-nitropyridin-2-amine;
    N-苯基乙基-6-甲砜基-3-硝基吡啶-2-胺；N-phenylethyl-6-methylsulfonyl-3-nitropyridin-2-amine;
    N-(2-氯苯基)乙基-6-甲亚砜基-3-硝基吡啶-2-胺；N-(2-chlorophenyl)ethyl-6-methylsulfoxide-3-nitropyridin-2-amine;
    N-(2-氯苯基)乙基-6-甲砜基-3-硝基吡啶-2-胺；N-(2-chlorophenyl)ethyl-6-methylsulfonyl-3-nitropyridin-2-amine;
    N-(4-氯苯基)乙基-6-甲亚砜基-3-硝基吡啶-2-胺；N-(4-chlorophenyl)ethyl-6-methylsulfoxide-3-nitropyridin-2-amine;
    N-(4-甲基苯基)乙基-6-甲亚砜基-3-硝基吡啶-2-胺；N-(4-methylphenyl)ethyl-6-methylsulfoxide-3-nitropyridin-2-amine;
    N-(4-甲氧基苯基)乙基-6-甲亚砜基-3-硝基吡啶-2-胺；N-(4-methoxyphenyl)ethyl-6-methylsulfoxide-3-nitropyridin-2-amine;
    N-乙基-6-乙砜基-3-硝基吡啶-2-胺；N-ethyl-6-ethylsulfonyl-3-nitropyridin-2-amine;
    N-乙基-6-异丙亚砜基-3-硝基吡啶-2-胺；N-ethyl-6-isopropylsulfoxide-3-nitropyridin-2-amine;
    N-乙基-6-异丙砜基-3-硝基吡啶-2-胺；N-ethyl-6-isopropylsulfonyl-3-nitropyridin-2-amine;
    N-乙基-6-丁亚砜基-3-硝基吡啶-2-胺；N-ethyl-6-butylsulfoxide-3-nitropyridin-2-amine;
    N-乙基-6-丁砜基-3-硝基吡啶-2-胺；N-ethyl-6-butsulfonyl-3-nitropyridin-2-amine;
    N-乙基-6-烯丙硫基-3-硝基吡啶-2-胺；N-ethyl-6-allylthio-3-nitropyridin-2-amine;
    N-乙基-6-烯丙亚砜基-3-硝基吡啶-2-胺；N-ethyl-6-allylsulfoxide-3-nitropyridin-2-amine;
    N-乙基-6-烯丙砜基-3-硝基吡啶-2-胺；N-ethyl-6-allylsulfonyl-3-nitropyridin-2-amine;
    N-乙基-6-炔丙硫基-3-硝基吡啶-2-胺；N-ethyl-6-propargylthio-3-nitropyridin-2-amine;
    N-乙基-6-炔丙亚砜基-3-硝基吡啶-2-胺；N-ethyl-6-propargyl sulfoxide-3-nitropyridin-2-amine;
    N-乙基-6-苯基甲亚砜基-3-硝基吡啶-2-胺；N-ethyl-6-phenylmethanesulfonyl-3-nitropyridin-2-amine;
    N-乙基-6-((氯(苯基)甲基)亚砜基)-3-硝基吡啶-2-胺；N-ethyl-6-((chloro(phenyl)methyl)sulfoxide)-3-nitropyridin-2-amine;
    N-环丙基-6-甲砜基-3-硝基吡啶-2-胺；N-cyclopropyl-6-methylsulfonyl-3-nitropyridin-2-amine;
    N1,N2-双(6-甲砜基-3-硝基吡啶-2-基)乙烷-1,2-二胺。N1,N2-bis(6-methylsulfonyl-3-nitropyridin-2-yl)ethane-1,2-diamine.
  6. 根据权利要求1所述的吡啶砜及其衍生物的制备方法，其特征在于式(I)所示的化合物通过下面所示的反应制备得到，The process for producing pyrithione and a derivative thereof according to claim 1, wherein the compound represented by the formula (I) is produced by the reaction shown below.
    反应式1：Reaction formula 1:
    Figure PCTCN2018123428-appb-100004
    Figure PCTCN2018123428-appb-100004
    反应式2：Reaction 2:
    Figure PCTCN2018123428-appb-100005
    Figure PCTCN2018123428-appb-100005
    在溶剂四氢呋喃、二氧六环、水、乙醇、甲醇、乙腈、二氯甲烷、二氯乙烷或N,N-二甲基甲酰胺中，于-10℃～体系回流温度，式(II)所示的化合物和式(III)所示的化合物反应，得式(I n＝0)所示的化合物；在溶剂二氯甲烷、二氯乙烷、四氢呋喃、二氧六环、水、乙醇、甲醇、乙腈或N,N-二甲基甲酰胺中，于-10℃～体系回流温度，式(I n＝0)所示的化合物经常规氧化剂间氯过氧苯甲酸、过氧化氢、过氧乙酸、次氯酸盐、草酸、过氧叔丁醇、过硫酸氢钾或过硼酸钠氧化，即可制得式(I n＝1,2)所示的化合物；In the solvent tetrahydrofuran, dioxane, water, ethanol, methanol, acetonitrile, dichloromethane, dichloroethane or N, N-dimethylformamide, at -10 ° C ~ system reflux temperature, formula (II) The compound shown is reacted with a compound of the formula (III) to give a compound of the formula (I n = 0); in a solvent of dichloromethane, dichloroethane, tetrahydrofuran, dioxane, water, ethanol, In methanol, acetonitrile or N,N-dimethylformamide, the compound represented by the formula (I n=0) is subjected to a conventional oxidizing agent, chloroperoxybenzoic acid, hydrogen peroxide, at a temperature of from -10 ° C to the reflux temperature of the system. Oxidizing with oxyacetic acid, hypochlorite, oxalic acid, potassium t-butanol, potassium hydrogen persulfate or sodium perborate to obtain a compound of the formula (I n=1, 2);
    在溶剂乙醇、甲醇、四氢呋喃、二氧六环、乙腈、二氯甲烷、二氯乙烷或N,N-二甲基 甲酰胺中，在没有碱或在碱碳酸钾、碳酸钠、三乙胺、吡啶、氢化钠、氢氧化钠或氢氧化钾存在下，用式(IV)所示的化合物和式(V)所示的化合物反应，得式(II)所示的化合物；In the solvent ethanol, methanol, tetrahydrofuran, dioxane, acetonitrile, dichloromethane, dichloroethane or N, N-dimethylformamide, in the absence of a base or in the alkali potassium carbonate, sodium carbonate, triethylamine In the presence of pyridine, sodium hydride, sodium hydroxide or potassium hydroxide, a compound of the formula (IV) and a compound of the formula (V) are reacted to obtain a compound of the formula (II);
    式中n、m、R、R 1、R 2、R 3、R 4和R 5具有权利要求1中所给定义，L是离去基团氯或溴,M为氢、钠或钾，其它取代基除特别指明外均如前所限定。 Wherein n, m, R, R 1 , R 2 , R 3 , R 4 and R 5 have the definitions given in claim 1, L is a leaving group chlorine or bromine, M is hydrogen, sodium or potassium, and the others Substituents are as defined above unless otherwise specified.
  7. 根据权利要求1～5任一项所述的吡啶砜及其衍生物的用途，其特征在于在15～5000克有效成分/公顷用量下具有杀菌和/或杀虫、杀螨生物活性。Use of pyridyl sulfone and a derivative thereof according to any one of claims 1 to 5, characterized in that it has bactericidal and/or insecticidal and acaricidal activity at an amount of from 15 to 5000 g of active ingredient per hectare.
  8. 根据权利要求1～5任一项所述的吡啶砜及其衍生物用于制备具有杀菌和/或杀虫、杀螨活性的药物的用途。Use of the pyrithione according to any one of claims 1 to 5 and a derivative thereof for the preparation of a medicament having bactericidal and/or insecticidal and acaricidal activity.
  9. 一种杀菌、杀虫或杀螨组合物，其特征在于：含有作为活性组分的如权利要求1～5任一项所述的吡啶砜及其衍生物，组合物中活性组分的重量百分含量为0.5-99％。A bactericidal, insecticidal or acaricidal composition comprising as an active ingredient the pyridine sulfone according to any one of claims 1 to 5 and a derivative thereof, the weight of the active ingredient in the composition The content of the fraction is 0.5-99%.
  10. 一种防治病菌或害虫/螨的方法，其特征在于：将有效量的如权利要求1～5任一项所述的吡啶砜及其衍生物施于所述病菌、害虫/螨、杂草或其生长介质上。A method for controlling a pathogen or a pest/clam, characterized in that an effective amount of the pyridyl sulfone according to any one of claims 1 to 5 and a derivative thereof are applied to the pathogen, pest, cockroach, weed or Its growth medium.
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